Multiple types of high-threshold calcium channels in rabbit sensory neurons: high-affinity block of neuronal L-type by nimodipine.
Whole-cell and cell-attached patch recording have been used to characterize multiple types of voltage-dependent calcium channels in neurons freshly dispersed from rabbit dorsal root ganglia. In whole-cell patch recordings, high-threshold current, strongly resistant to inactivation by depolarized holding potentials (L-type; V1/2 = -27.2 mV), was potently inhibited by nimodipine. Assuming 1:1 binding, the dissociation constant for nimodipine binding to the inactivated state of the L-type calcium channel (KI) was 5.3 nM (n = 8). In contrast, a second type of high-threshold current less resistant to inactivation by depolarized holding potentials (N-type; V1/2 = -56.9 mV) was not blocked by nimodipine. Nimodipine-resistant N-type calcium current was inhibited by omega-conotoxin (5 microM). Cell-attached patch recordings of single calcium channel currents demonstrated the existence of three different unitary conductances; 7.4 pS, 13.1 pS, and 24.1 pS. The 24.1 pS high-threshold channel was enhanced by (-) BAY K 8644 and inhibited by nimodipine in a concentration- and voltage-dependent manner. Hyperpolarization reversed this block. These results demonstrate that, as in cardiac and smooth muscle, there is a component of neuronal high-threshold current corresponding to the L-type calcium channel that can be blocked with high affinity by nimodipine.
McCarthy
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RT
Miles Institute for Preclinical Pharmacology, West Haven, Connecticut 06516.
TanPiengco
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PE
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004056:Differential Threshold; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D004594:Electrophysiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology*; D011817:Rabbits
D015220:Calcium Channels; D009553:Nimodipine