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Papers by Daniel Weinreich

Research paper thumbnail of Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)

Molecular vision, 2017

Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its... more Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline's post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)-neuroprotective ability. We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in fl...

Research paper thumbnail of Ca(2+)-induced Ca2+ release mediates Ca2+ transients evoked by single action potentials in rabbit vagal afferent neurones

The Journal of Physiology, 1997

1. Standard intracellular recording techniques with ‘sharp’ micropipettes were used to evoke acti... more 1. Standard intracellular recording techniques with ‘sharp’ micropipettes were used to evoke action potentials (APs) in acutely dissociated adult nodose neurones. 2. APs induced a transient increase in [Ca2+]i (a calcium transient), recorded with fura‐2, that was dependent upon [Ca2+]o and the number of APs. Over the range of one to sixty‐five APs, the relation between the amplitude of the calcium transient and the number of APs was well fitted by a rectangular hyperbola (chi 2 = 3.53, r = 0.968). From one to four APs, the calcium transient‐AP relation can be described by a line with a slope of 9.6 nM AP‐1 (r = 0.999). 3. Charge movement corresponding to Ca2+ influx evoked by a single AP was 39 +/‐ 2.8 pC (mean +/‐ S.E.M.) and did not change significantly during trains of one to thirty‐one APs (P < 0.05). 4. Caffeine (10 mM), a known agonist of the ryanodine receptor, produced an increase in [Ca2+]i. The caffeine‐induced rise in [Ca2+]i was attenuated (by > 90%) by lowering [C...

Research paper thumbnail of Synaptic plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hypertension

American Journal of …, 2001

plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hyperten... more plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hypertension. Am J Physiol Regulatory Integrative Comp Physiol 281: R635-R644, 2001.-Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP (tL) were increased and correlated with blood pressure (slope ϭ 0.15 min/mmHg, r ϭ 0.52, P Ͻ 0.047 and 6.7 min/mmHg, r ϭ 0.906, P Ͻ 0.0001, respectively). In BOS and OHR, tL (minutes) was 492 Ϯ 40 (n ϭ 7) and 539 Ϯ 41 (n ϭ 5), respectively, and differed (P Ͻ 0.05) from BOR (257 Ϯ 48, n ϭ 4), SD vehicle rats (240 Ϯ 18, n ϭ 4), and captopril-treated OHR (370 Ϯ 52, n ϭ 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and tL in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP. neurons; angiotensin; breeding; sodium pump; captopril; long-term potentiation INCREASED SYMPATHETIC NERVE ACTIVITY (SNA) has been implicated in the development and maintenance of

Research paper thumbnail of Sexually dimorphic regulation of NK-1 receptor-mediated electrophysiological responses in vagal primary afferent neurons

Journal of neurophysiology, 2000

Neurons can display sexual dimorphism in receptor expression, neurotransmitter release, and synap... more Neurons can display sexual dimorphism in receptor expression, neurotransmitter release, and synaptic plasticity. We have detected sexual dimorphism in functional tachykinin receptors in vagal afferents (nodose ganglion neurons, NGNs) by studying the effects of hormonal variation on the depolarizing actions of substance P (SP) in female guinea pig NGNs. Using conventional "sharp" microelectrode recording plus measurement of serum 17beta-estradiol values, we examined SP responses in NGNs isolated from 1) ovariectomized females (OVX), 2) OVX females treated with 17beta-estradiol (OVX + E2), 3) pregnant females, and 4) males. Depending on various manipulations, 19-41% female NGNs were depolarized (16 +/- 1.1 mV, mean +/- SE) by 100 nM SP acting through NK-1 receptors. The NGNs of OVX + E2 females (41%, 15/37; 17 +/- 2.1 mV) and pregnant females (41%, 32/79; 16 +/- 1.7 mV) were more likely to respond to SP than those of control males (P < 0.001). The percentage of SP-sensiti...

Research paper thumbnail of The determination of picomole levels of 5-hydroxytryptamine and dopamine inAplysia, Tritonia and leech nervous tissues

Brain Res, 1973

... W. McCAMAN, D. WEINREICH AND RE McCAMANDivision of Neurosciences, City of Hope National Medic... more ... W. McCAMAN, D. WEINREICH AND RE McCAMANDivision of Neurosciences, City of Hope National Medical Center, Duarte, Calif. ... proportional to the amount of DA up to 400 pmoles.The recovery of DA added to tissue extracts was 50-80 %; estimations of DA in sam-ples were ...

Research paper thumbnail of Effects of long-term organ culture on neurotransmitter metabolism in the ganglia ofAplysia californica

J Neurobiol, 1974

The abdominal and pedal-pleural ganglia of Aplysia californica were maintained in organ culture f... more The abdominal and pedal-pleural ganglia of Aplysia californica were maintained in organ culture for periods up t o 45 days. Neurophysiological examination of abdominal ganglia indicated that synaptic activity could be evoked in ganglia cultured for 21 days and action potentials and spontaneous postsynaptic potentials persisted for 45 days. The effects of long-term culture on neurotransmitter metabolism were studied by measuring the activities of ChAc, AChE, AAD, and COMT in both cultured abdominal and pedal-pleural ganglia. G-6-PD and CarnAc activities were also measured. In general, the stabilities of the enzymes in abdominal ganglia to in vitro conditions were similar to those in pedal-pleural ganglia. None of the enzymes studied were markedly affected by culture conditions for a t least fourteen days. After this time, enzymes involved in neurotransmitter synthesis, AAD and ChAc, exhibited fairly abrupt decreases in activity. The degradative enzymes studied, AChE and COMT, showed more gradual decreases in activity. The changes occurring in the neurotransmitter metabolizing enzymes after prolonged periods of time in culture are discussed in relation t o the neurophysiological changes which were observed.

Research paper thumbnail of Angiotensin II increases excitability and inhibits a transient potassium current in vagal primary sensory neurons

Neuropeptides, Jun 1, 2009

The octapeptide angiotensin II (ANG II) plays a pivotal role in the maintenance of blood pressure... more The octapeptide angiotensin II (ANG II) plays a pivotal role in the maintenance of blood pressure by activating ANG II receptors located in variety of cell types including neurons housed in the central nervous system (CNS) and in the peripheral nervous system (PNS). ANG II (100 nM) blocked spike frequency accommodation (SFA) recorded with whole-cell patch technique in acutely isolated nodose ganglion neurons (NGN) from adult rats. ANG II increased the frequency of action potentials (AP) produced by supramaximal 500 ms depolarizing currents recorded in both tonic (16 Hz vs. 58 Hz, control vs. ANG II perfusion respectively, n = 9) and phasic (1 Hz vs. 38 Hz, n = 13) NGNs. ANG II produced no significant changes in: the resting membrane potential (À51 mV vs. À50 mV, n = 65), AP overshoot (46 mV vs. 41 mV, n = 25), AP undershoot (À65 mV vs. À61 mV, n = 25), AP duration (1 ms vs. 1.2 ms, n = 25), and AP threshold (À40 mV vs. À43 mV, n = 19). CV-11974 (600 nM), a specific AT1 receptor antagonist, prevented ANG II-evoked changes SFA (n = 10). ANG II (100 nM) had no significant effect on total outward potassium current (I K) but inhibited a fast activating and fast inactivating I K recorded in the presence of TEA. A kinetically similar I K was also inhibited by 4-AP (3 mM). In phasic NGNs, 4-AP occluded the effects of 100 nM ANG II on SFA. Our results indicate that ANG II can block an A-type of I K and that this effect may underlie the ANG II-mediated change in SFA.

Research paper thumbnail of Neuroimmune interactions in the lung

The primary role of the immune system is to protect the host against pathogens. Until recently it... more The primary role of the immune system is to protect the host against pathogens. Until recently it has been thought that the immune system functioned in isolation, however, it has become increasingly evident that the immune system and, in particular, the nervous system are functionally interconnected. In this review we describe various interactions between the nervous and immune systems in the lung. Particular attention will be given to the interactions of neuropeptide mediators from the nonadrenergic, non-cholinergic (NANC) sensory nervous system with mast cells, macrophages and eosinophils, and the special role that nerve growth factor (NGF) plays in these interactions.

Research paper thumbnail of A perfusion chamber for physiological studies with acutely dissociated neurons

Journal of Neuroscience Methods, Nov 30, 1987

We describe a recording chamber that immobilizes acutely dissociated neurons on an ultra-fine mes... more We describe a recording chamber that immobilizes acutely dissociated neurons on an ultra-fine mesh grid positioned above a moving stream of perfusate. This chamber is easily fabricated and has two attributes for single-electrode voltage-clamp or patch-clamp recording: (1) shallow immersion (< 20 #m) of the neurons, and (2) stable recording with rapid perfusion rates.

Research paper thumbnail of Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia

The American Journal of Physiology, 1991

Research paper thumbnail of An In Vitro Characterization of ?-Glutamylhistamine Synthetase: A Novel Enzyme Catalyzing Histamine Metabolism in the Central Nervous System of the Marine Mollusk, Aplysia californica

Research paper thumbnail of Presynaptic and postsynaptic effects of histamine and histamine agonists in the superior cervical ganglion of the rat

Neuropharmacology, Jul 31, 1987

Extracellular and intracellular recording techniques were used to study the effects of histamine ... more Extracellular and intracellular recording techniques were used to study the effects of histamine and the histamine agonists [impromidine (IMP) and 2-thiazolylethylamine (2-TH)] on synaptic transmission in the superior cervical ganglion of the rat in vitro. At the concentrations employed (up to 10(-5) M) these compounds did not produce detectable effects on the electrical properties of the postsynaptic neurons. Histamine produced a dose-dependent reduction in the amplitude of the extracellularly-recorded presynaptic and postsynaptic compound action potential. The H2 receptor agonist impromidine reduced only the postganglionic compound action potential. Cimetidine, a specific H2 receptor antagonist, produced parallel shifts in the log dose-response curves for impromidine. Impromidine also reduced the average size of the evoked excitatory postsynaptic potential. The reduction of the mean amplitude of the excitatory postsynaptic potential was due to a decrease in the amount of acetylcholine (ACh) liberated by each preganglionic volley (mean quantal content, m) and a diminution in quantal size. The H1 receptor agonist, 2-TH produced a dose-dependent increase in the presynaptic and postsynaptic compound action potential and in m. The increase in m was not associated with changes in quantal size. The H1 antagonists, pyrilamine and promethazine, did not prevent facilitation of ganglionic transmission induced by 2-TH. It is concluded that histamine H1 and H2 receptors exist on preganglionic axons, or terminals in sympathetic ganglia of the rat. Activation of H1 receptors facilitates release of ACh whereas H2 receptor activation results in depressed release.

Research paper thumbnail of Role of calcium in regulating primary sensory neuronal excitability

Handbook of experimental pharmacology, 2009

The fundamental role of calcium ions (Ca(2+)) in an excitable tissue, the frog heart, was first d... more The fundamental role of calcium ions (Ca(2+)) in an excitable tissue, the frog heart, was first demonstrated in a series of classical reports by Sydney Ringer in the latter part of the nineteenth century (1882a, b; 1893a, b). Even so, nearly a century elapsed before it was proven that Ca(2+) regulated the excitability of primary sensory neurons. In this chapter we review the sites and mechanisms whereby internal and external Ca(2+) can directly or indirectly alter the excitability of primary sensory neurons: excitability changes being manifested typically by variations in shape of the action potential or the pattern of its discharge.

Research paper thumbnail of Substance P hyperpolarizes vagal sensory neurones of the ferret

The Journal of physiology, Jan 15, 1996

1. Intracellular recordings were made in intact and in acutely dissociated vagal afferent neurone... more 1. Intracellular recordings were made in intact and in acutely dissociated vagal afferent neurones (nodose ganglion cells) of the ferret to investigate the effects of substance P(SP). 2. In current-clamp recordings, SP (100 nM) applied by superfusion hyperpolarized the membrane potential (7 +/- 0.7 mV; mean +/- S.E.M.; n = 105) and decreased the input resistance in 80% of the neurones. With voltage-clamp recording, SP produced an outward current of 3 +/- 0.2 nA (n = 10). 3. The SP current was concentration dependent with an estimated EC50 of 68 nM. The SP-induced hyperpolarization or current was mimicked by the tachykinin receptor NK1 agonist Ac-[Arg6, Sar9, Met(O2)11]SP(6-11) (ASM-SP; 100 nM; n = 10) and blocked by the NK1 antagonist CP-96,345 (10 nM; n = 6), but not by the NK2 antagonist SR48968 (100 nM; n = 4). No measurable change in membrane potential or input resistance was observed with application of either [beta-Ala8]neurokinin A or senktide, selective NK2 and NK3 receptor ...

Research paper thumbnail of Bradykinin decreases K(+) and increases Cl(-) conductances in vagal afferent neurones of the guinea pig

The Journal of physiology, Jan 15, 2004

Bradykinin (BK) is an inflammatory mediator that can excite and sensitize primary afferent neuron... more Bradykinin (BK) is an inflammatory mediator that can excite and sensitize primary afferent neurones. The nature of the ionic channels underlying the excitatory actions of BK is still incompletely understood. Using whole-cell patch-clamp recording from acutely dissociated nodose ganglion neurones (NGNs) we have examined the ionic mechanism responsible for BK's excitatory effect. Bath-applied BK (0.1 microM) depolarized the membrane potential (29 +/- 3.1 mV, n= 7), evoked action potentials, and induced an inward ionic current (I(BK)) with two distinctive membrane conductances (g(m)). Initially, g(m) decreased; the ionic current associated with this g(m) had a reversal potential (E(rev)) value of -87 +/- 1.1 mV (n= 26), a value close to E(K) (-89 mV). Subsequently, g(m) increased; the ionic current associated with this g(m) had an estimated E(rev) of 49 +/- 4.3 mV (n= 23). When the second component was isolated from the first component, by replacing [K(+)](o) with Cs(+), E(rev) was...

Research paper thumbnail of Calcium signaling in single peripheral sensory nerve terminals

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2003

Peripheral sensory nerve terminals (PSNTs) have a dual function: reporting normal and abnormal se... more Peripheral sensory nerve terminals (PSNTs) have a dual function: reporting normal and abnormal sensations and releasing trophic factors to maintain the structure and function of epithelial cells. Although it is widely considered that intracellular Ca2+ plays a critical signaling role for both functions, the role of Ca2+ signaling has never been studied in PSNTs, primarily because of their small size and anatomical inaccessibility. Here, using epifluoresence microscopy and a fluorescent Ca2+ indicator, we report that action potentials or chemical irritation can elicit transient rises in [Ca2+]i (Ca2+ transients) in PSNTs within the corneal epithelium of the rat. In vitro electrical stimulation of the ciliary nerves in the eye, or electrical field stimulation of the cornea, evoked Ca2+ transients with a magnitude that was proportional to the number of stimuli applied over the range of 1-10 stimuli. Ca2+ transients were significantly blocked by 1 mm lidocaine, 4.1 microm saxitoxin (STX...

Research paper thumbnail of Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain

The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003

The underlying mechanisms of neuropathic pain are poorly understood, and existing treatments are ... more The underlying mechanisms of neuropathic pain are poorly understood, and existing treatments are mostly ineffective. We recently demonstrated that antisense mediated "knock-down" of the sodium channel isoform, Na(V)1.8, reverses neuropathic pain behavior after L5/L6 spinal nerve ligation (SNL), implicating a critical functional role of Na(V)1.8 in the neuropathic state. Here we have investigated mechanisms through which Na(V)1.8 contributes to the expression of experimental neuropathic pain. Na(V)1.8 does not appear to contribute to neuropathic pain through an action in injured afferents because the channel is functionally downregulated in the cell bodies of injured neurons and does not redistribute to injured terminals. Although there was little change in Na(V)1.8 protein or functional channels in the cell bodies of uninjured neurons in L4 ganglia, there was a striking increase in Na(V)1.8 immunoreactivity along the sciatic nerve. The distribution of Na(V)1.8 reflected pr...

Research paper thumbnail of Coexistence of functional IP(3) and ryanodine receptors in vagal sensory neurons and their activation by ATP

Journal of neurophysiology, 2002

Intracellular photorelease of caged D-myo-inositol 1,4,5-trisphosphate (IP(3)), caffeine applicat... more Intracellular photorelease of caged D-myo-inositol 1,4,5-trisphosphate (IP(3)), caffeine application, and immunofluorescence confocal microscopy were used to determine that D-myo-inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) coexist in rabbit vagal sensory nodose ganglion neurons (NGNs). ATP, an extracellular physiological signaling molecule, consistently evoked robust transient increases in cytosolic free Ca(2+) concentration (Ca(2+) transients). ATP applied in Ca(2+)-free physiological saline elicited Ca(2+) transients that averaged approximately 70% of the amplitude of transients evoked in the presence of extracellular Ca(2+). The component of the ATP-evoked Ca(2+) transient that was independent of extracellular Ca(2+) corresponds to Ca(2+) release from intracellular stores. This release component was sensitive to the pharmacological antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), U73122, neomycin, and heparin (...

Research paper thumbnail of Chemical communication between vagal afferent somata in nodose Ganglia of the rat and the Guinea pig in vitro

Journal of neurophysiology, 2002

The cell bodies of spinal afferents, dorsal root ganglion neurons, are depolarized several milliv... more The cell bodies of spinal afferents, dorsal root ganglion neurons, are depolarized several millivolts, and their probability of spiking increased when axons of neighboring somata in the same ganglion are electrically stimulated repetitively. This form of neural communication has been designated cross-depolarization (CD) and cross-excitation (CE). The existence of CD and CE between somata of vagal afferents (nodose ganglion neurons, NGNs) of rats and guinea pigs was investigated by electrically stimulating the vagus nerve while recording the electrical activity of NGNs in intact nodose ganglia with sharp intracellular microelectrodes. CD and CE in NGNs were manifested by a membrane depolarization (approximately 4 mV), the presence of spontaneous action potentials, and a decreased spike threshold. CD was dependent on the frequency and intensity of vagal nerve stimulation. Two distinct types of CD were observed: 1) in NGNs with large input resistances (R(in)), CD was dependent on [Ca2+...

Research paper thumbnail of 5-HT(3) receptors mediate inflammation-induced unmasking of functional tachykinin responses in vitro

Journal of applied physiology (Bethesda, Md. : 1985), 2002

Exogenously applied tachykinins produce no measurable electrophysiological responses in the somat... more Exogenously applied tachykinins produce no measurable electrophysiological responses in the somata of vagal afferent neurons [nodose ganglion neurons (NGNs)] isolated from naive guinea pigs. By contrast, after in vitro antigen challenge of nodose ganglia from guinea pigs immunized with chick ovalbumin, approximately 60% (53 of 89) of NGNs were depolarized an average of 13 +/- 1.2 mV by substance P (SP; 100 nM; n = 53). Receptor antagonists and enzyme inhibitors were utilized to screen a number of mast cell-derived mediators for their role in the uncovering or "unmasking" of functional tachykinin receptors after antigen challenge. Two chemically distinct 5-hydroxytryptamine-3-receptor antagonists significantly reduced the percentage of NGNs displaying depolarizing SP responses. Treatment with Y-25130 (1 or 10 microM) or tropisetron (1 microM) 15 min before and during antigen challenge reduced the percentage of SP-responsive neurons to approximately 20 and approximately 15% ...

Research paper thumbnail of Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)

Molecular vision, 2017

Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its... more Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline's post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)-neuroprotective ability. We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in fl...

Research paper thumbnail of Ca(2+)-induced Ca2+ release mediates Ca2+ transients evoked by single action potentials in rabbit vagal afferent neurones

The Journal of Physiology, 1997

1. Standard intracellular recording techniques with ‘sharp’ micropipettes were used to evoke acti... more 1. Standard intracellular recording techniques with ‘sharp’ micropipettes were used to evoke action potentials (APs) in acutely dissociated adult nodose neurones. 2. APs induced a transient increase in [Ca2+]i (a calcium transient), recorded with fura‐2, that was dependent upon [Ca2+]o and the number of APs. Over the range of one to sixty‐five APs, the relation between the amplitude of the calcium transient and the number of APs was well fitted by a rectangular hyperbola (chi 2 = 3.53, r = 0.968). From one to four APs, the calcium transient‐AP relation can be described by a line with a slope of 9.6 nM AP‐1 (r = 0.999). 3. Charge movement corresponding to Ca2+ influx evoked by a single AP was 39 +/‐ 2.8 pC (mean +/‐ S.E.M.) and did not change significantly during trains of one to thirty‐one APs (P < 0.05). 4. Caffeine (10 mM), a known agonist of the ryanodine receptor, produced an increase in [Ca2+]i. The caffeine‐induced rise in [Ca2+]i was attenuated (by > 90%) by lowering [C...

Research paper thumbnail of Synaptic plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hypertension

American Journal of …, 2001

plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hyperten... more plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hypertension. Am J Physiol Regulatory Integrative Comp Physiol 281: R635-R644, 2001.-Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP (tL) were increased and correlated with blood pressure (slope ϭ 0.15 min/mmHg, r ϭ 0.52, P Ͻ 0.047 and 6.7 min/mmHg, r ϭ 0.906, P Ͻ 0.0001, respectively). In BOS and OHR, tL (minutes) was 492 Ϯ 40 (n ϭ 7) and 539 Ϯ 41 (n ϭ 5), respectively, and differed (P Ͻ 0.05) from BOR (257 Ϯ 48, n ϭ 4), SD vehicle rats (240 Ϯ 18, n ϭ 4), and captopril-treated OHR (370 Ϯ 52, n ϭ 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and tL in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP. neurons; angiotensin; breeding; sodium pump; captopril; long-term potentiation INCREASED SYMPATHETIC NERVE ACTIVITY (SNA) has been implicated in the development and maintenance of

Research paper thumbnail of Sexually dimorphic regulation of NK-1 receptor-mediated electrophysiological responses in vagal primary afferent neurons

Journal of neurophysiology, 2000

Neurons can display sexual dimorphism in receptor expression, neurotransmitter release, and synap... more Neurons can display sexual dimorphism in receptor expression, neurotransmitter release, and synaptic plasticity. We have detected sexual dimorphism in functional tachykinin receptors in vagal afferents (nodose ganglion neurons, NGNs) by studying the effects of hormonal variation on the depolarizing actions of substance P (SP) in female guinea pig NGNs. Using conventional "sharp" microelectrode recording plus measurement of serum 17beta-estradiol values, we examined SP responses in NGNs isolated from 1) ovariectomized females (OVX), 2) OVX females treated with 17beta-estradiol (OVX + E2), 3) pregnant females, and 4) males. Depending on various manipulations, 19-41% female NGNs were depolarized (16 +/- 1.1 mV, mean +/- SE) by 100 nM SP acting through NK-1 receptors. The NGNs of OVX + E2 females (41%, 15/37; 17 +/- 2.1 mV) and pregnant females (41%, 32/79; 16 +/- 1.7 mV) were more likely to respond to SP than those of control males (P < 0.001). The percentage of SP-sensiti...

Research paper thumbnail of The determination of picomole levels of 5-hydroxytryptamine and dopamine inAplysia, Tritonia and leech nervous tissues

Brain Res, 1973

... W. McCAMAN, D. WEINREICH AND RE McCAMANDivision of Neurosciences, City of Hope National Medic... more ... W. McCAMAN, D. WEINREICH AND RE McCAMANDivision of Neurosciences, City of Hope National Medical Center, Duarte, Calif. ... proportional to the amount of DA up to 400 pmoles.The recovery of DA added to tissue extracts was 50-80 %; estimations of DA in sam-ples were ...

Research paper thumbnail of Effects of long-term organ culture on neurotransmitter metabolism in the ganglia ofAplysia californica

J Neurobiol, 1974

The abdominal and pedal-pleural ganglia of Aplysia californica were maintained in organ culture f... more The abdominal and pedal-pleural ganglia of Aplysia californica were maintained in organ culture for periods up t o 45 days. Neurophysiological examination of abdominal ganglia indicated that synaptic activity could be evoked in ganglia cultured for 21 days and action potentials and spontaneous postsynaptic potentials persisted for 45 days. The effects of long-term culture on neurotransmitter metabolism were studied by measuring the activities of ChAc, AChE, AAD, and COMT in both cultured abdominal and pedal-pleural ganglia. G-6-PD and CarnAc activities were also measured. In general, the stabilities of the enzymes in abdominal ganglia to in vitro conditions were similar to those in pedal-pleural ganglia. None of the enzymes studied were markedly affected by culture conditions for a t least fourteen days. After this time, enzymes involved in neurotransmitter synthesis, AAD and ChAc, exhibited fairly abrupt decreases in activity. The degradative enzymes studied, AChE and COMT, showed more gradual decreases in activity. The changes occurring in the neurotransmitter metabolizing enzymes after prolonged periods of time in culture are discussed in relation t o the neurophysiological changes which were observed.

Research paper thumbnail of Angiotensin II increases excitability and inhibits a transient potassium current in vagal primary sensory neurons

Neuropeptides, Jun 1, 2009

The octapeptide angiotensin II (ANG II) plays a pivotal role in the maintenance of blood pressure... more The octapeptide angiotensin II (ANG II) plays a pivotal role in the maintenance of blood pressure by activating ANG II receptors located in variety of cell types including neurons housed in the central nervous system (CNS) and in the peripheral nervous system (PNS). ANG II (100 nM) blocked spike frequency accommodation (SFA) recorded with whole-cell patch technique in acutely isolated nodose ganglion neurons (NGN) from adult rats. ANG II increased the frequency of action potentials (AP) produced by supramaximal 500 ms depolarizing currents recorded in both tonic (16 Hz vs. 58 Hz, control vs. ANG II perfusion respectively, n = 9) and phasic (1 Hz vs. 38 Hz, n = 13) NGNs. ANG II produced no significant changes in: the resting membrane potential (À51 mV vs. À50 mV, n = 65), AP overshoot (46 mV vs. 41 mV, n = 25), AP undershoot (À65 mV vs. À61 mV, n = 25), AP duration (1 ms vs. 1.2 ms, n = 25), and AP threshold (À40 mV vs. À43 mV, n = 19). CV-11974 (600 nM), a specific AT1 receptor antagonist, prevented ANG II-evoked changes SFA (n = 10). ANG II (100 nM) had no significant effect on total outward potassium current (I K) but inhibited a fast activating and fast inactivating I K recorded in the presence of TEA. A kinetically similar I K was also inhibited by 4-AP (3 mM). In phasic NGNs, 4-AP occluded the effects of 100 nM ANG II on SFA. Our results indicate that ANG II can block an A-type of I K and that this effect may underlie the ANG II-mediated change in SFA.

Research paper thumbnail of Neuroimmune interactions in the lung

The primary role of the immune system is to protect the host against pathogens. Until recently it... more The primary role of the immune system is to protect the host against pathogens. Until recently it has been thought that the immune system functioned in isolation, however, it has become increasingly evident that the immune system and, in particular, the nervous system are functionally interconnected. In this review we describe various interactions between the nervous and immune systems in the lung. Particular attention will be given to the interactions of neuropeptide mediators from the nonadrenergic, non-cholinergic (NANC) sensory nervous system with mast cells, macrophages and eosinophils, and the special role that nerve growth factor (NGF) plays in these interactions.

Research paper thumbnail of A perfusion chamber for physiological studies with acutely dissociated neurons

Journal of Neuroscience Methods, Nov 30, 1987

We describe a recording chamber that immobilizes acutely dissociated neurons on an ultra-fine mes... more We describe a recording chamber that immobilizes acutely dissociated neurons on an ultra-fine mesh grid positioned above a moving stream of perfusate. This chamber is easily fabricated and has two attributes for single-electrode voltage-clamp or patch-clamp recording: (1) shallow immersion (< 20 #m) of the neurons, and (2) stable recording with rapid perfusion rates.

Research paper thumbnail of Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia

The American Journal of Physiology, 1991

Research paper thumbnail of An In Vitro Characterization of ?-Glutamylhistamine Synthetase: A Novel Enzyme Catalyzing Histamine Metabolism in the Central Nervous System of the Marine Mollusk, Aplysia californica

Research paper thumbnail of Presynaptic and postsynaptic effects of histamine and histamine agonists in the superior cervical ganglion of the rat

Neuropharmacology, Jul 31, 1987

Extracellular and intracellular recording techniques were used to study the effects of histamine ... more Extracellular and intracellular recording techniques were used to study the effects of histamine and the histamine agonists [impromidine (IMP) and 2-thiazolylethylamine (2-TH)] on synaptic transmission in the superior cervical ganglion of the rat in vitro. At the concentrations employed (up to 10(-5) M) these compounds did not produce detectable effects on the electrical properties of the postsynaptic neurons. Histamine produced a dose-dependent reduction in the amplitude of the extracellularly-recorded presynaptic and postsynaptic compound action potential. The H2 receptor agonist impromidine reduced only the postganglionic compound action potential. Cimetidine, a specific H2 receptor antagonist, produced parallel shifts in the log dose-response curves for impromidine. Impromidine also reduced the average size of the evoked excitatory postsynaptic potential. The reduction of the mean amplitude of the excitatory postsynaptic potential was due to a decrease in the amount of acetylcholine (ACh) liberated by each preganglionic volley (mean quantal content, m) and a diminution in quantal size. The H1 receptor agonist, 2-TH produced a dose-dependent increase in the presynaptic and postsynaptic compound action potential and in m. The increase in m was not associated with changes in quantal size. The H1 antagonists, pyrilamine and promethazine, did not prevent facilitation of ganglionic transmission induced by 2-TH. It is concluded that histamine H1 and H2 receptors exist on preganglionic axons, or terminals in sympathetic ganglia of the rat. Activation of H1 receptors facilitates release of ACh whereas H2 receptor activation results in depressed release.

Research paper thumbnail of Role of calcium in regulating primary sensory neuronal excitability

Handbook of experimental pharmacology, 2009

The fundamental role of calcium ions (Ca(2+)) in an excitable tissue, the frog heart, was first d... more The fundamental role of calcium ions (Ca(2+)) in an excitable tissue, the frog heart, was first demonstrated in a series of classical reports by Sydney Ringer in the latter part of the nineteenth century (1882a, b; 1893a, b). Even so, nearly a century elapsed before it was proven that Ca(2+) regulated the excitability of primary sensory neurons. In this chapter we review the sites and mechanisms whereby internal and external Ca(2+) can directly or indirectly alter the excitability of primary sensory neurons: excitability changes being manifested typically by variations in shape of the action potential or the pattern of its discharge.

Research paper thumbnail of Substance P hyperpolarizes vagal sensory neurones of the ferret

The Journal of physiology, Jan 15, 1996

1. Intracellular recordings were made in intact and in acutely dissociated vagal afferent neurone... more 1. Intracellular recordings were made in intact and in acutely dissociated vagal afferent neurones (nodose ganglion cells) of the ferret to investigate the effects of substance P(SP). 2. In current-clamp recordings, SP (100 nM) applied by superfusion hyperpolarized the membrane potential (7 +/- 0.7 mV; mean +/- S.E.M.; n = 105) and decreased the input resistance in 80% of the neurones. With voltage-clamp recording, SP produced an outward current of 3 +/- 0.2 nA (n = 10). 3. The SP current was concentration dependent with an estimated EC50 of 68 nM. The SP-induced hyperpolarization or current was mimicked by the tachykinin receptor NK1 agonist Ac-[Arg6, Sar9, Met(O2)11]SP(6-11) (ASM-SP; 100 nM; n = 10) and blocked by the NK1 antagonist CP-96,345 (10 nM; n = 6), but not by the NK2 antagonist SR48968 (100 nM; n = 4). No measurable change in membrane potential or input resistance was observed with application of either [beta-Ala8]neurokinin A or senktide, selective NK2 and NK3 receptor ...

Research paper thumbnail of Bradykinin decreases K(+) and increases Cl(-) conductances in vagal afferent neurones of the guinea pig

The Journal of physiology, Jan 15, 2004

Bradykinin (BK) is an inflammatory mediator that can excite and sensitize primary afferent neuron... more Bradykinin (BK) is an inflammatory mediator that can excite and sensitize primary afferent neurones. The nature of the ionic channels underlying the excitatory actions of BK is still incompletely understood. Using whole-cell patch-clamp recording from acutely dissociated nodose ganglion neurones (NGNs) we have examined the ionic mechanism responsible for BK's excitatory effect. Bath-applied BK (0.1 microM) depolarized the membrane potential (29 +/- 3.1 mV, n= 7), evoked action potentials, and induced an inward ionic current (I(BK)) with two distinctive membrane conductances (g(m)). Initially, g(m) decreased; the ionic current associated with this g(m) had a reversal potential (E(rev)) value of -87 +/- 1.1 mV (n= 26), a value close to E(K) (-89 mV). Subsequently, g(m) increased; the ionic current associated with this g(m) had an estimated E(rev) of 49 +/- 4.3 mV (n= 23). When the second component was isolated from the first component, by replacing [K(+)](o) with Cs(+), E(rev) was...

Research paper thumbnail of Calcium signaling in single peripheral sensory nerve terminals

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2003

Peripheral sensory nerve terminals (PSNTs) have a dual function: reporting normal and abnormal se... more Peripheral sensory nerve terminals (PSNTs) have a dual function: reporting normal and abnormal sensations and releasing trophic factors to maintain the structure and function of epithelial cells. Although it is widely considered that intracellular Ca2+ plays a critical signaling role for both functions, the role of Ca2+ signaling has never been studied in PSNTs, primarily because of their small size and anatomical inaccessibility. Here, using epifluoresence microscopy and a fluorescent Ca2+ indicator, we report that action potentials or chemical irritation can elicit transient rises in [Ca2+]i (Ca2+ transients) in PSNTs within the corneal epithelium of the rat. In vitro electrical stimulation of the ciliary nerves in the eye, or electrical field stimulation of the cornea, evoked Ca2+ transients with a magnitude that was proportional to the number of stimuli applied over the range of 1-10 stimuli. Ca2+ transients were significantly blocked by 1 mm lidocaine, 4.1 microm saxitoxin (STX...

Research paper thumbnail of Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain

The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003

The underlying mechanisms of neuropathic pain are poorly understood, and existing treatments are ... more The underlying mechanisms of neuropathic pain are poorly understood, and existing treatments are mostly ineffective. We recently demonstrated that antisense mediated "knock-down" of the sodium channel isoform, Na(V)1.8, reverses neuropathic pain behavior after L5/L6 spinal nerve ligation (SNL), implicating a critical functional role of Na(V)1.8 in the neuropathic state. Here we have investigated mechanisms through which Na(V)1.8 contributes to the expression of experimental neuropathic pain. Na(V)1.8 does not appear to contribute to neuropathic pain through an action in injured afferents because the channel is functionally downregulated in the cell bodies of injured neurons and does not redistribute to injured terminals. Although there was little change in Na(V)1.8 protein or functional channels in the cell bodies of uninjured neurons in L4 ganglia, there was a striking increase in Na(V)1.8 immunoreactivity along the sciatic nerve. The distribution of Na(V)1.8 reflected pr...

Research paper thumbnail of Coexistence of functional IP(3) and ryanodine receptors in vagal sensory neurons and their activation by ATP

Journal of neurophysiology, 2002

Intracellular photorelease of caged D-myo-inositol 1,4,5-trisphosphate (IP(3)), caffeine applicat... more Intracellular photorelease of caged D-myo-inositol 1,4,5-trisphosphate (IP(3)), caffeine application, and immunofluorescence confocal microscopy were used to determine that D-myo-inositol 1,4,5-trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) coexist in rabbit vagal sensory nodose ganglion neurons (NGNs). ATP, an extracellular physiological signaling molecule, consistently evoked robust transient increases in cytosolic free Ca(2+) concentration (Ca(2+) transients). ATP applied in Ca(2+)-free physiological saline elicited Ca(2+) transients that averaged approximately 70% of the amplitude of transients evoked in the presence of extracellular Ca(2+). The component of the ATP-evoked Ca(2+) transient that was independent of extracellular Ca(2+) corresponds to Ca(2+) release from intracellular stores. This release component was sensitive to the pharmacological antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), U73122, neomycin, and heparin (...

Research paper thumbnail of Chemical communication between vagal afferent somata in nodose Ganglia of the rat and the Guinea pig in vitro

Journal of neurophysiology, 2002

The cell bodies of spinal afferents, dorsal root ganglion neurons, are depolarized several milliv... more The cell bodies of spinal afferents, dorsal root ganglion neurons, are depolarized several millivolts, and their probability of spiking increased when axons of neighboring somata in the same ganglion are electrically stimulated repetitively. This form of neural communication has been designated cross-depolarization (CD) and cross-excitation (CE). The existence of CD and CE between somata of vagal afferents (nodose ganglion neurons, NGNs) of rats and guinea pigs was investigated by electrically stimulating the vagus nerve while recording the electrical activity of NGNs in intact nodose ganglia with sharp intracellular microelectrodes. CD and CE in NGNs were manifested by a membrane depolarization (approximately 4 mV), the presence of spontaneous action potentials, and a decreased spike threshold. CD was dependent on the frequency and intensity of vagal nerve stimulation. Two distinct types of CD were observed: 1) in NGNs with large input resistances (R(in)), CD was dependent on [Ca2+...

Research paper thumbnail of 5-HT(3) receptors mediate inflammation-induced unmasking of functional tachykinin responses in vitro

Journal of applied physiology (Bethesda, Md. : 1985), 2002

Exogenously applied tachykinins produce no measurable electrophysiological responses in the somat... more Exogenously applied tachykinins produce no measurable electrophysiological responses in the somata of vagal afferent neurons [nodose ganglion neurons (NGNs)] isolated from naive guinea pigs. By contrast, after in vitro antigen challenge of nodose ganglia from guinea pigs immunized with chick ovalbumin, approximately 60% (53 of 89) of NGNs were depolarized an average of 13 +/- 1.2 mV by substance P (SP; 100 nM; n = 53). Receptor antagonists and enzyme inhibitors were utilized to screen a number of mast cell-derived mediators for their role in the uncovering or "unmasking" of functional tachykinin receptors after antigen challenge. Two chemically distinct 5-hydroxytryptamine-3-receptor antagonists significantly reduced the percentage of NGNs displaying depolarizing SP responses. Treatment with Y-25130 (1 or 10 microM) or tropisetron (1 microM) 15 min before and during antigen challenge reduced the percentage of SP-responsive neurons to approximately 20 and approximately 15% ...