An R-type Ca2+ current in neurohypophysial terminals preferentially regulates oxytocin secretion

Multiple types of voltage-dependent Ca2+ channels are involved in the regul ation of neurotransmitter release (Tsien et al., 1991; Dunlap et al., 1995) . In the nerve terminals of the neurohypophysis, the roles of L-, N-, and P /Q-type Ca2+ channels in neuropeptide release have been identified previous ly (Wang et al., 1997a). Although the L- and N- type Ca2+ currents play equ ivalent roles in both vasopressin and oxytocin release, the P/Q- type Ca2current only regulates vasopressin release. An oxytocin-release and Ca2+ cu rrent component is resistant to the L-, N-, and P/Q-type Ca2+ channel block ers but is inhibited by Ni2+. A new polypeptide toxin, SNX-482, which is a specific alpha(1E) -type Ca2+ channel blocker (Newcomb et al., 1998), was u sed to characterize the biophysical properties of this resistant Ca2+ curre nt component and its role in neuropeptide release. This resistant component was dose dependently inhibited by SNX-482, with an IC50 of 4.1 nM. Further more, SNX-482 did not affect the other Ca2+ current types in these CNS term inals. Like the N- and P/Q- type Ca2+ currents, this SNX-482-sensitive tran sient Ca2+ current is high-threshold activated and shows moderate steady-st ate inactivation. At the same concentrations, SNX-482 blocked the component of oxytocin, but not of vasopressin, release that was resistant to the oth er channel blockers, indicating a preferential role for this type of Ca2+ c urrent in oxytocin release from neurohypophysial terminals. Our results sug gest that an alpha(1E) or "R"- type Ca2+ channel exists in oxytocinergic ne rve terminals and, thus, functions in controlling only oxytocin release fro m the rat neurohypophysis.