Calcium Channels that Are Required for Secretion from Intact Nerve Terminals of Vertebrates Are Sensitive to ~0-Conotoxin and Relatively Insensitive to Dihydropyridines Optical Studies with and without Voltage-sensitive Dyes

Extrinsic absorption changes exhibited by potentiometric dyes have established the ionic basis of the action potential in synchronously activated populations of nerve terminals in the intact neurohypophyses of amphibia and mammals (Salzberg et al., 1983; Obaid et al., 1983, 1985b). Also, large and rapid changes in light scattering, measured as transparency, have been shown to follow membrane depolarization and to be intimately associated with the release of neuropeptides from the nerve terminals of the mouse neurohypophysis (Salzberg et al., 1985; Gainer et al., 1986). We report some experiments that help to define the pharmacological profile of the calcium channels present in intact neurosecretory terminals of vertebrates. For these, we used the peptide toxin t0-conotoxin GVIA (1-5 #M) and the dihydropyridine compounds Bay-K 8644 and nifedipine (2-5 #M), together with the after-hyperpolarization of the nerve terminal action potential. This undershoot depends upon the activation of a calcium-mediated potassium channel, as suggested by its sensitivity to [Ca++]o and charybdotoxin, o~conotoxin GVIA substantially reduced the after-hyperpolarization in neurosecretory terminals of Xenopus, while neither of the dihydropyridine compounds had any effect under conditions that mimic natural stimulation. The effects of these calcium channel modifiers on the action potential recorded optically from the terminals of the Xenopus neurohypophysis were faithfully reflected in the behavior of Address reprint requests to Dr. B. M. Salzberg, Department of Physiology, University of Pennsylvania, School of Medicine, A201 Richards Building, Philadelphia, PA 19104-6085. Dr. Flores' present address is Unite-29-Institut Nationale de la Sant6 et de la Recherche Medicale, Hopital de Port-Royal, 123, Boulevard de Port-Royal, F-75014 Paris, France. J. G~N. PHYSIOL. ~) The Rockefeller University Press 9 0022-1295/89/04/0715/15 $2.00 Volume 93 April 1989 715-729 715 on Jne 4, 2017 D ow nladed fom Published April 1, 1989