Bradykinin decreases K(+) and increases Cl(-) conductances in vagal afferent neurones of the guinea pig (original) (raw)
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Bradykinin-induced ion currents in cultured rat trigeminal ganglion cells
Neuroscience Research, 1993
Effects of bradykinin (BK) on membrane currents of cultured rat trigeminal ganglion cells were studied with a GO-sealed discontinuous voltage clamp technique. Bradykinin (0.05 nM-1/~M) produced membrane depolarization in most cells and hyperpolarization in some cells via a variety of ionic mechanisms: (1) activation of a cation current, (2) enhancement or (3) inhibition of a hyperpolarization-activated inwardly rectifying cation current known as I H, (4) reduction or (5) enhancement of an outwardly rectifying outward current (presumably a delayed K ÷ current), (6) inhibition of a slow-gating voltage-dependent steady-state outward current (at >-55 mV) and/or (7) increase in another slow-gating voltage-dependent outward current (at >/-70 mV). These components of BK-induced currents appeared in different combinations and extents among cells, explaining complex excitatory and modulatory actions of BK in different regions and types of sensory neurons.
Multiple Ionic Mechanisms Activated by Bradykinin in Coronary Venular Endothelial Cells
In coronary endothelium, bradykinin (BK) modulates production of vasodilators by stimulating Ca2+ influx. To examine the ionic currents involved in this process, we applied BK (100 nM) to single bovine coronary venular endothelial cells (CVEC) while recording membrane potential (Em)o r whole-cell current simultaneously with [Ca2+li. The resting potential (Er) of unstimulated cells was bimodally distributed (-70 ± 9 mV, n = 26; -15 ± 8 mV, n = 30). Irrespective of E, BK evoked a biphasic [Ca2+Iiin crease simultaneously with a change in Em. When Er was negative to -30 mV, depolarizations were typically observed. When Er was positive to -30 mV, transient hyperpolarizations were typically observed. Under voltage clamp, [Ca2+] increased as the membrane hyperpolarized and the ratio A[Ca*+Ii/AE, was greater in the presence of BK than in unstimulated cells. Many, but not all, cells exhibited an outward K+ current that appeared to be Ca2+ dependent. When present, this current typically prp dominated over other currents and resulted in hyperpolarizations. When K+ currents were small or blocked, two inward curwnts were recorded. The first was a large (-224 f 20 pA at -70 mV), rapidly activating current carried by C1-. The second was a smaller (-81 f 9 pA at -70 mV) cationic current carried in part by Ca2+. These data suggest that BK activates at least three distinct currents in CVECs: a K+-current, a C1--current, and a nonselective cation current. The predominance of one or more of these currents in an individual cell presumably determines that cell‘s electrophysiological response to BK.
The Journal of Physiology, 2001
Bradykinin (Bk) is released when the kallikrein-kinin system is activated during tissue stress or damage (Raidoo & Bhoola, 1998). It is an important mediator of pain and inflammation (Dray & Perkins, 1993; Dray, 1997; Millan, 1999). Bk-evoked pain is due, at least partly, to direct activation of B 2 receptors that are expressed constitutively by nociceptive sensory neurones (Dray & Perkins, 1993). The B 2 receptors are coupled to phosphoinositidase C and Bk-induced pain and/or hyperalgesia probably involves phosphorylation of plasma membrane ion channels by protein kinase C-e (Burgess et al. 1989; Cesare et al. 1999). Receptors for Bk are not only found on neurones but are expressed by a wide range of cell types (Farmer & Burch, 1992). For example, Bk receptors are expressed by non-neuronal cells such as glial cells (Stephens et al. 1993) and fibroblasts (Estacion, 1991) but the role, if any, played by non-neuronal cells in the pro-inflammatory effects of Bk is not clear. Schwann cells in dorsal root ganglia (DRG) release glutamate in response to Bk (Parpura et al. 1995) and fibroblasts release prostaglandin E 2 (Lerner et al. 1992) so it is reasonable to suppose that indirect effects of Bk on non-neuronal cells might contribute to the response of the sensory neurones. There is also good evidence that B 1 receptors, which are induced during inflammation, mediate Bk-induced hyperalgesia and/or allodynia but it is unclear whether these receptors are located primarily on neurones (Eckert et al. 1999) or on non-neuronal tissues (Davis et al. 1996). In the present study we describe responses to Bk of small fibroblast-like satellite (FLS) cells isolated from neonatal rat DRG. These cells are usually associated with the somata of DRG neurones and they proliferate in culture after acute dissociation of ganglia. It has previously been shown that peri-somatic non-neuronal satellite cells proliferate in DRG during local inflammation or following peripheral axotomy (Lu & Richardson, 1991) but little is known of their contribution to neuronal signalling either in normal tissue or under pathological
Bradykinin inhibits a slow spike afterhyperpolarization in visceral sensory neurons
European Journal of Pharmacology, 1986
Intracellular recordings were made from visceral sensory neurons in vitro. Bradykinin (BK) depressed a slow CaZ+-activated K+-dependent (Kca) spike afterhyperpolarization (AHp,) in the range of 0.2-1 nM. BK did not affect the fast Kca spike afterhyperpolarization preceding the AHP s or the action potential waveform. Indomethacin pretreatment abolished the BK effect. These results indicate that BK can influence the excitability of vagal afferent neurons.
Bradykinin-induced potassium current in cultured bovine aortic endothelial cells
The Journal of Membrane Biology, 1990
Bovine aortic endothelial cells (BAECs) respond to bradykinin with an increase in cytosolic-free Ca 2+ concentration, [Ca2+]i, accompanied by an increase in surface membrane K* permeability. In this study, electrophysiological measurement of K + current was combined with 86Rb ~ efflux measurements to characterize the K" flux pathway in BAECs. Bradykinin-and Ca2+-activated K + currents were identified and shown to be blocked by the alkylammonium compound, tetrabutylammonium chloride and by the scorpion toxin, noxiustoxin, but not by apamin or tetraethylammonium chloride. Whole-cell and singlechannel current analysis suggest that the threshold for Ca 2+ activation is in the range of 10 to 100 nM [Ca2+]~. The whole-cell current measurements show voltage sensitivity only at the membrane potentials more positive than 0 mV where significant current decay occurs during a sustained depolarizing pulse. Another K + current present in control conditions, an inwardly rectifying K + current, was blocked by Ba 2+ and was not affected by noxiustoxin or tetrabutylammonium chloride. Effiux of ~6Rb-from BAEC monolayers was stimulated by both bradykinin and ionomycin. Stimulated efflux was blocked by tetrabutyl-and tetrapentyl-ammonium chloride and by noxiustoxin, but not by apamin or furosemide. Thus, S6Rb+ efflux stimulated by bradykinin and ionomycin has the same pharmacological sensitivity as the bradykinin-and Ca2+-activated membrane currents. The results confirm that bradykinin-stimulated 86Rb+ efflux occurs via CaZ--activated K + channels. The blocking agents identified may provide a means for interpreting the role of the Ca2*-actirated K + current in the response of BAECs to bradykinin.
European Biophysics Journal, 2005
Bradykinin (BK) excites dorsal root ganglion cells, leading to the sensation of pain. The actions of BK are thought to be mediated by heterotrimeric G proteinregulated pathways. Indeed there is strong evidence that in different cell types BK is involved in phosphoinositide breakdown following activation of G q/11 . In the present study we show that the Ca 2+ current flowing through Ltype voltage-gated Ca 2+ channels in NG108-15 cells (differentiated in vitro to acquire a neuronal phenotype), measured using the whole-cell patch clamp configuration, is reversibly inhibited by BK in a voltage-independent fashion, suggesting a cascade process where a second messenger system is involved. This inhibitory action of BK is mimicked by the application of 1,2oleoyl-acetyl glycerol (OAG), an analog of diacylglycerol that activates PKC. Interestingly, OAG occluded the effects of BK and both effects were blocked by selective PKC inhibitors. The down modulation of single L-type Ca 2+ channels by BK and OAG was also investigated in cell-attached patches. Our results indicate that the inhibitory action of BK involves activation of PKC and mainly shows up in a significant reduction of the probability of channel opening, caused by an increase and clustering of null sweeps in response to BK.
Journal of neurophysiology, 2014
Little is known about electrophysiological differences of A-type transient K(+) (KA) currents in nociceptive afferent neurons that innervate somatic and visceral tissues. Staining with isolectin B4 (IB4)-FITC classifies L6-S1 dorsal root ganglion (DRG) neurons into three populations with distinct staining intensities: negative to weak, moderate, and intense fluorescence signals. All IB4 intensely stained cells are negative for a fluorescent dye, Fast Blue (FB), injected into the bladder wall, whereas a fraction of somatic neurons labeled by FB, injected to the external urethral dermis, is intensely stained with IB4. In whole-cell, patch-clamp recordings, phrixotoxin 2 (PaTx2), a voltage-gated K(+) (Kv)4 channel blocker, exhibits voltage-independent inhibition of the KA current in IB4 intensely stained cells but not the one in bladder-innervating cells. The toxin also shows voltage-independent inhibition of heterologously expressed Kv4.1 current, whereas its inhibition of Kv4.2 and K...