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Journal of Neuroscience, Vol 12, 2225-2234, Copyright © 1992 by Society for Neuroscience
Multiple types of high-threshold calcium channels in rabbit sensory neurons: high-affinity block of neuronal L-type by nimodipine
RT McCarthy and PE TanPiengco
Miles Institute for Preclinical Pharmacology, West Haven, Connecticut 06516.
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.
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