Long-term regulation of neuronal calcium current by prolonged changes of membrane potential (original) (raw)
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Long-term regulation of neuronal calcium currents by prolonged changes of membrane potential
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1992
Although rapid-onset, short-term regulation of neuronal Ca currents by neurotransmitters and second messengers is well documented, little is known about conditions that can cause longer-lasting changes in Ca channel function. We report here that persistent depolarization is accompanied by slowly developing long-term reduction of neuronal Ca currents. Rat myenteric neurons grown in cell culture for 1-7 d were studied with the tight-seal whole-cell recording technique. Macroscopic Ca-channel currents had decaying and sustained components at all days studied. When the neurons were grown in medium containing 25 mM KCl, which depolarized them to -40 mV and caused significant elevation of intracellular Ca, the densities of both components of Ca-channel current decreased by 40-80%. Several results suggest that different mechanisms underlie the downregulation of the two components. (1) The density of the decaying component decreased approximately four times faster than did that of the susta...
Calcium currents in cultured rat cortical neurons
Brain Research, 1989
Rat neocortical neurons grown in dissociated cell culture for 4-12 weeks were studied with whole-cell patch-clamp techniques in order to characterize the calcium currents present in these cells. When voltage-dependent Na and K currents were inhibited, depolarizations from negative holding potentials induced inward currents which had 3 components: a low threshold activated, small, relatively persistent component, which was completely inactivated at holding potentials more positive then-60 mV; a higher threshold, relatively persistent component (which was not inactivated at VH =-50 mV); and a higher threshold, larger, transient component. All 3 components were reduced by removal of Ca, and blocked by Cd and Ni at appropriate concentrations. The components were differentially affected by low concentrations of Ni (500/~M), nifedipine (500/~M) and Ba (1.8 mM). Only the first two components were present in very young neurons.
Persistent Ca2+Current Contributes to a Prolonged Depolarization inAplysiaBag Cell Neurons
Journal of Neurophysiology, 2009
Neurons may initiate behavior or store information by translating prior activity into a lengthy change in excitability. For example, brief input to the bag cell neurons of Aplysia results in an approximate 30-min afterdischarge that induces reproduction. Similarly, momentary stimulation of cultured bag cells neurons evokes a prolonged depolarization lasting many minutes. Contributing to this is a voltage-independent cation current activated by Ca2+entering during the stimulus. However, the cation current is relatively short-lived, and we hypothesized that a second, voltage-dependent persistent current sustains the prolonged depolarization. In bag cell neurons, the inward voltage-dependent current is carried by Ca2+; thus we tested for persistent Ca2+current in primary culture under voltage clamp. The observed current activated between −40 and −50 mV exhibited a very slow decay, presented a similar magnitude regardless of stimulus duration (10–60 s), and, like the rapid Ca2+current, ...
Intracellular Calcium and Control of Burst Generation in Neurons of Guinea-Pig Neocortex in Vitro
European Journal of Neuroscience, 1989
Response properties of neurons in brain slices of guinea pig parietal neocortex were examined following intracellular injection of the Ca2+ chelators, EGTA and BAPTA. Although chelator injection did not cause any consistent change in passive membrane properties, it did induce 81% of neurons encountered at all sub-pial depths to become 'bursters', in that just-threshold depolarizing current pulses triggered all-or-none bursts of 2-5 fast action potentials. Transition to 'burstiness' was associated with disappearance of an AHP and appearance of a DAP. Although chelator caused a slight increase in steady-state firing rate, marked accommodation persisted. Extracellular Co2+ or Mn2+ had an effect on steady-state firing rate similar to that of the intracellular chelators; however, exposure to these Ca2+ channel blockers also caused steady state depolarization, increased resting input resistance and time constant, and profound spike broadening. This treatment never induced transition to 'burstiness'. Chelator-injected neurons ceased to generate bursts when Ca2+ was replaced by Mn2+ in the Ringer's solution. During exposure to 50-200 msec Ca2+ spikes followed brief depolarizing pulses. As chelator was injected into the cell, there was progressive prolongation of the Ca2' plateaus, which was associated with slowing of the rate at which membrane resistance gradually recovered following the initial increase in conductance. activate processes which prevent most neocortical neurons from being bursters. These processes probably include Ca2+-dependent K + currents, and Ca2+-dependent Ca2+ channel inactivation. M TTX and 20 mM TEA, These findings indicate that under normal conditions, activity-related increases in intracellular Ca2' Correspondence to; M. J. Gutnick, as above
Pfl�gers Archiv European Journal of Physiology, 1992
The kinetic, permeability and pharmacological properties of Ca currents were investigated in primary cultures of rat hippocampal neurons. The low-voltage-activated (LVA) Ca current turned on positive to -60 mV and fully inactivated in a voltage-dependent way. This current was depressed by nickel (Ni, 40~tM) and amiloride (500 IxM) and was insensitive to 09-conotoxin (09-CgTx) (4 ~tM) and to the Ca agonist Bay K 8644 (5 ~tM). The high-voltage-activated (HVA) Ca current turned on positive to -40 mV and inactivated slowly and incompletely. This current was much less sensitive than the LVA current to Ni and amiloride but more sensitive to cadmium. r blocked only partially this current (about 50%) in an irreversible way. Bay K 8644 had a clear agonistic action almost exclusively on the 09-CgTx-resistant HVA current component. The present resuits suggest that the HVA channels, quite homogeneous for their kinetic properties and sensitivity to holding potentials, can be pharmacologically separated in two classes: (i) 09-CgTx-sensitive and Bay-K-8644-insensitive (09-S/BK-I) and (ii) 09-CgTx-insensitive and Bay-K-8644sensitive (09-I/BK-S), the latter displaying a stronger Cadependent inactivation.
Modulation of Voltage-Dependent Calcium Channels in Cultured Neuronsa
Annals of the New York Academy of Sciences, 2006
In many types of excitable cells there are several classes of voltage-dependent calcium channels (VDCC) as determined by the characteristic properties of single channel activity. A clear distinction exists between low conductance channels, activated by moderate depolarizations (low voltage-activated, LVA), and high conductance channels activated by large depolarizations (high voltage-activated, HVA).'" In cardiac tissue these were termed T and L channels, respectively, because they were found to be pharmacologically as well as biophysically distinct.' Because of this, they can also be clearly differentiated in whole-cell current recordings.'" Evidence also exists for a third class of single channel conductance (N type) whose biophysical properties were originally described as being intermediate between T and L and which appears to be expressed only in cells of neuronal origin.ss The sensitivity of N-type channels to irreversible block by w-conotoxin GVIA (w-CgTx)' and the large number of w-CgTx binding sites in neuronal tissue indicate that they are likely to be important for neuronal function! High threshold Caz+ currents insensitive to both w-CgTx and dihydropyridines have been reported:' and a selective blocker for at least part of this current is the peptide toxin from Agelenopsis aperta, w-agatoxin IVA (w-aga IVA). The current inhibited by this toxin has been termed P current, because Purkinje cells express calcium channel currents that are largely resistant to w-CgTx and 1P-dihydropyridines (DHPs): and these currents are sensitive to w-aga IVA.* It is difficult to distinguish these currents by biophysical means at the whole cell l e~e l , 5 "~ and although estimates of their single channel conductances indicate differences, this is complicated by the existence of subconductance states.'O However, prolongation of single channel open times by DHP agonists remains diagnostic of L channels.'' aThe work in this laboratory was supported by the Wellcome Trust and MRC.
The Journal of Physiology
1. Using the whole-cell recording mode of the patch-clamp technique, we have investigated kinetic and selectivity properties of a low-voltage-activated (l.v.a.) Ca2+ current in chick and rat dorsal root ganglion (d.r.g.) neurones. 2. L.v.a currents were activated at about-50 mV and reached maximum amplitudes between-30 and-20 mV with averages of-0-16 nA in chick and-03 nA in rat d.r.g. cells with 5 mM-extracellular Ca2+. Between-60 and-20 mV, the time to peak, tp, of this current decreased with increasing membrane depolarizations. An e-fold change of tp required a 14 mV potential change in chick and a 17 mV change in rat d.r.g. cells at 22 'C. 3. Between-50 and + 20 mV inactivation of this current was fast, single exponential and voltage dependent. In rat, the time constant of inactivation, Th, was smaller and less voltage dependent than in chick. 4. The amplitude of these currents increased by a factor of 5-10, when the extracellular Ca2+ concentration was changed from 1 to 95 mm. Amplitudes and kinetic parameters of the currents showed typical shifts along the voltage axis. No correlation between Ca2+ current amplitudes and activation-inactivation kinetics was found, suggesting that the reaction rates which control these processes are not dependent on Ca2+ entry. 5. Recovery from inactivation was voltage dependent and developed with a time constant, Tr' in the order of 1 s. Tr was nearly halved by changing the potential from-80 to-120 mV. 6. Tail currents associated with membrane repolarization were also voltage dependent and developed exponentially. Their time constant decreased by a factor of 3 when the potential was changed from-60 to-100 mV. 7. A second and more prominent Ca2+ current was activated at potentials positive to-20 mV (high-voltage-activated Ca2+ currents, h.v.a.), masking the time course of l.v.a. currents. Between-20 and 0 mV, time to peak of the entire current increased by a factor of 2 but decreased again at higher membrane potentials. Inactivation also became significantly slower in this potential range.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994
Ca2+ currents in acutely isolated, adult rat neostriatal neurons were studied with whole-cell voltage-clamp techniques. In the vast majority of neurons (approximately 90%, n > 250), currents were exclusively of the high-voltage-activated (HVA) type. HVA currents activated near -40 mV and reached their maximum amplitude near 0 mV. Quasi-steady-state inactivation curves in many neurons were well fitted only with a sum of Boltzmann functions, suggesting that the HVA currents were heterogeneous. Although the block of whole-cell current by Cd2+ was well fitted with a single isotherm having an IC50 of near 1 microM, experiments with organic channel antagonists suggested that at least four types of HVA channels were expressed by most cells. On average, the L-channel antagonist nifedipine (5-10 microM) blocked 31 +/- 10% of the whole-cell current (n = 20), the N-channel antagonist omega-conotoxin GVIA (omega-CgTx) (2-5 microM) blocked 27 +/- 11% (n = 20), and the P-channel antagonist ome...