Barbiturates and nifedipine have different and selective effects on calcium currents of mouse DRG neurons in culture: a possible basis for differing clinical actions. The 1987 S. Weir Mitchell award

Abstract

Barbiturates and dihydropyridines have been shown to block voltage-dependent calcium channels, but have differing sites of action and clinical effects. We have investigated the effects of the barbiturates, pentobarbital and phenobarbital, and the dihydropyridine, nifedipine, on isolated calcium currents in mouse dorsal root ganglion neurons in culture. Three different calcium channels exist in neurons, designated T, N, and L. None of the drugs affected the T calcium current, but all blocked the activation of the L calcium current. Nifedipine had no effect on the N calcium current. The activation of the N calcium current from holding potentials more negative than--80 mV was not affected by either barbiturate, though both caused a more rapid inactivation of the current at test potentials of--20 to 0 mV. To determine the possible functional significance of these different and selective effects on calcium currents, we studied synaptically driven spontaneous activity in spinal cord neurons in culture. Nifedipine had no effect on spontaneous activity, whereas pentobarbital completely suppressed it. This suggests that block of the L calcium channel alone is not sufficient to suppress spontaneous activity. The additional action of pentobarbital on N calcium current may explain in part the complete suppression of spontaneous activity; other possibilities are discussed. These data suggest a basis for the separate sites of action of barbiturates and dihydropyridines as well as a possible mechanism for the hypnotic and anesthetic effects of the barbiturates.