Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons

Plummer, Mark R.; Logothetis, Diomedes E.; Hess, Peter

doi:10.1016/0896-6273(89)90191-8

Cited by 653 publications

(560 citation statements)

References 30 publications

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“…However, it seems unlikely that w-CgTX is blocking an L-type current in our experiments because, like cultured Xenopus neurons (Barish,199 l), acutely isolated Xenopus neurons either do not possess or only have a very small dihydropyridinesensitive Ca*+ current (N. Dale, unpublished observation). It is possible that w-CgTX is reversibly blocking a subtype of N-like channels; for example, Ellinor et al (1993) have recently described a rapidly inactivating Ca2+ current that is reversibly blocked by o-CgTX and Plummer et al (1989) have described a component of N-type Ca*+ current that is reversibly blocked by w-CgTX in peripheral neurons. Resolution of this problem awaits the availability of agents that can discriminate between the components of the w-CgTX-sensitive current.…”

Section: Discussionmentioning

confidence: 99%

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord

Wall

Dale

1994

J. Neurosci.

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Activation of GABAB receptors in the Xenopus embryo, a simple vertebrate, causes presynaptic inhibition of transmitter release from glycinergic spinal neurons and an increase in action potential threshold. To investigate the underlying mechanisms of GABAB receptor action, we have made whole-cell voltage-clamp recordings from acutely isolated Xenopus embryo spinal neurons. The GABAB receptor agonist baclofen caused a reversible reduction in the amplitude of Ca2+ currents. This reduction of Ca2+ currents appeared to be voltage dependent as it was removed at very positive potentials. Since the specific GABAB antagonists CGP35348, phaclofen, and 2-hydroxysaclofen all blocked the reduction in Ca2+ currents, we concluded that the modulation of the Ca2+ current was mediated by GABAB receptors. We have investigated the pharmacological identity of the Ca2+ current modulated by baclofen using the selective blocker omega-conotoxin, fraction GVIA (omega-CgTX). omega-CgTX selectively blocked voltage-gated Ca2+ currents without affecting the voltage-gated Na+ current. omega-CgTX substantially occluded the action of baclofen, suggesting that GABAB receptors modulate an omega-CgTX-sensitive Ca2+ current. Since GABAB receptors mediate presynaptic inhibition, we have studied the involvement of the omega-CgTX-sensitive Ca2+ current in synaptic transmission in the intact spinal cord. Inhibitory interneuron axons were stimulated to evoke monosynaptic IPSPs in motoneurons, and recorded intracellularly. Since omega-CgTX blocked inhibitory transmission, we concluded that the omega-CgTX-sensitive Ca2+ current plays an essential role in transmitter release. If modulation of this current were to occur in nerve terminals, it could contribute to the GABAB receptor-mediated presynaptic inhibition of transmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord

Wall

Dale

1994

J. Neurosci.

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“…The outward current at strong depolarizations is presumably carried by the Cs present in the internal pipette solution (Lee and Tsien, 1982). The majority of calcium current in the chick sympathetic neurons appears to be carried by N-type Ca*+ channels (Nowycky et al, 1985;Plummer et al, 1989). Thus, application of nifedipine (10 PM), a blocker of L-type Ca 2+ channels, had little effect on the Ca2+ current elicited by a step to 0 mV from a holding potential of -60 mV (mean decrease of 12.5 f 10.5%, mean + SEM; n = 4).…”

Section: Ss and Ne Inhibit High-threshold Calcium Currentsmentioning

confidence: 99%

Kinetic basis for the voltage-dependent inhibition of N-type calcium current by somatostatin and norepinephrine in chick sympathetic neurons

Golard

Siegelbaum

1993

J. Neurosci.

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Neurotransmitter inhibition of calcium currents (ICa) can be relieved by large depolarizing prepulses. This effect has been postulated to be due either to the voltage-dependent unbinding of an inhibitory molecule from the channel or to a slow voltage-dependent gating step intrinsic to the modulated channel. According to the first hypothesis, the rate of reinhibition (reblock) following a depolarizing prepulse should depend on the concentration of active inhibitory molecules and thus should increase with the extent of inhibition. To distinguish between these models we examined the actions of norepinephrine (NE) and somatostatin (SS) on high-threshold calcium currents in chick sympathetic ganglia, using whole-cell voltage-clamp methods. As previously described in other systems, both NE and SS inhibit omega- conotoxin-sensitive N-type Ca2+ current in a voltage-dependent manner. Pertussis toxin (PTX) pretreatment prevents the inhibition of the current, while replacing GTP in the patch pipette with GTP-gamma-S results in irreversible inhibition, consistent with the involvement of a PTX-sensitive G-protein. The inhibitory responses to NE and SS are not additive, suggesting that they act at a common locus. The inhibitory response to repeated applications of NE or SS desensitizes, with little evidence for cross desensitization. The inhibition of ICa is relieved by a 15 msec prepulse to +100 mV. Following repolarization to -80 mV, ICa slowly reblocks. During prolonged applications of NE or SS the extent of inhibition decreases due to desensitization and reblock kinetics are significantly slowed (time constant increases from 60 msec to > 100 msec for both NE and SS). These results are well fit by a quantitative model in which the kinetics of reblock reflect the binding of an inhibitory molecule to the channel.

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“…The non-L-, non-N-type channel described here has a high probability of being recorded in patches of -CTx-GVIA-treated cells bathed in nifedipine and, therefore, is associated with the Q-like current that contributes to most of the residual non-L, non-N-type current in RINm5F cells [18]. Despite its distinctive pharmacology, the Q-like channel exhibits only subtle differences in the kinetics and permeability properties of the N-type channel of peripheral neurons [24], but deviates partially from the P-type channel of Purkinje neurons [34] and most significantly from the L-type channel of pancreaticcells [32].…”

Section: Discussionmentioning

confidence: 88%

“…The channel is best characterized by its resistance to DHPs and -CTx-GVIA and is shown to coexist with the more common L-type channel observed in various -cells and -cell lines [27,28,35]. Few outside-out patch recordings also provide evidence for a -CTx-GVIA-sensitive Ca 2+ channel with single-channel properties close to the N-type channel described in peripheral neurons [8,24]. The non-L-, non-N-type channel described here has a high probability of being recorded in patches of -CTx-GVIA-treated cells bathed in nifedipine and, therefore, is associated with the Q-like current that contributes to most of the residual non-L, non-N-type current in RINm5F cells [18].…”

Section: Discussionmentioning

confidence: 97%

“…Apart from this, the N-type channel of RINm5F cells displays close similarities to the N-type channel of other cells. In peripheral neurons the channel activates above 910 mV in 100 mM [Ba 2+ ] o , exhibits a 20 pS singlechannel conductance (1.3 pA at + 10 mV), inactivates weakly during prolonged depolarizations and possesses marked sensitivity to holding potential [24]. Indeed, the neuronal N-type channel also exhibits multiple gating modes with low and high p o [8], small and large conductance and slow and fast inactivation [23] that make any further comparison more complicated and arbitrary.…”

Section: Discussionmentioning

confidence: 99%

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A single non-L-, non-N-type Ca2+ channel in rat insulin-secreting RINm5F cells

Magnelli¹,

Avaltroni²,

Carbone³

1996

Pflugers Arch.

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Single high-voltage-activated (HVA) Ca 2+ channel activity was recorded in rat insulinoma RINm5F cells using cell-attached and outside-out configurations. Single-channel recordings revealed three distinct Ca 2+ channel subtypes : one sensitive to dihydropyridines (DHPs)-(L-type), another sensitive to -conotoxin (CTx)-GVIA (N-type) and a third type insensitive to DHPs and -CTx-GVIA (non-L-, non-N-type). The L-type channel was recorded in most patches between 930 and +30 mV. The channel had pharmacological and biophysical features similar to the L-type channels described in other insulin-secreting cells (mean conductance 21 pS in control conditions and 24 pS in the presence of 5 µM Bay K 8644). The non-L-, non-N-type channel was recorded in cells chronically treated with -CTx-GVIA in the presence of nifedipine to avoid the contribution of N-and L-type channels. Channel activity was hardly detectable below 910 mV and was recruited by negative holding potentials (< 990 mV). The channel open probability increased steeply from 910 to + 40 mV. Different unitary current sublevels could be detected and the current voltage relationship was calculated from the higher amplitude level with a slope conductance of 21 pS. Channel activity lasted throughout depolarizations of 300-800 ms with little sign of inactivation. Above 0 mV the channel showed a persistent flickering kinetics with brief openings ( o 0.6 ms) and long bursts ( burst 60 ms) interrupted by short interburst intervals. The third HVA Ca 2+ channel subtype, the N-type, had biophysical properties similar to the non-L-, non-N-type and was best identified in outside-out patches by its sensitivity to -CTx-GVIA. The channel was detectable only above 910 mV from a 990 mV holding potential, exhibited a fast flickering behaviour, persisted during prolonged depolarizations and had a slope conductance of about 19 pS. The present data provide direct evidence for a slowly inactivating non-L-, non-N-type channel in insulin-secreting RINm5F cells that activates at more positive voltages than the L-type channel and indicate the possibility of identifying unequivocally single HVA Ca 2+ channels in cellattached and excised membrane patches under controlled pharmacological conditions.

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Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons

Cited by 653 publications

References 30 publications

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord

GABAB receptors modulate an omega-conotoxin-sensitive calcium current that is required for synaptic transmission in the Xenopus embryo spinal cord

Kinetic basis for the voltage-dependent inhibition of N-type calcium current by somatostatin and norepinephrine in chick sympathetic neurons

A single non-L-, non-N-type Ca2+ channel in rat insulin-secreting RINm5F cells

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