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The Journal of Neuroscience, November 1, 1999, 19(21):9235-9241

An R-Type Ca²⁺ Current in Neurohypophysial Terminals Preferentially Regulates Oxytocin Secretion

Gang Wang¹, Govindan Dayanithi², Robert Newcomb³, and José R. Lemos¹

¹ Department of Physiology and Neuroscience Program, University of Massachusetts Medical School, Worcester, Massachusetts 01655, ² UPR9055-CNRS, Biologie des Neurones Endocrines, Montpellier, Cedex 5, France, and ³ Elan Pharmaceuticals, Menlo Park, California 94025

Multiple types of voltage-dependent Ca²⁺ channels are involved in the regulation 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 previously (Wang et al., 1997a). Although the L- and N-type Ca²⁺ currents play equivalent roles in both vasopressin and oxytocin release, the P/Q-type Ca²⁺ current only regulates vasopressin release. An oxytocin-release and Ca²⁺ current component is resistant to the L-, N-, and P/Q-type Ca²⁺ channel blockers but is inhibited by Ni²⁺. A new polypeptide toxin, SNX-482, which is a specific _1E-type Ca²⁺ channel blocker (Newcomb et al., 1998), was used to characterize the biophysical properties of this resistant Ca²⁺ current component and its role in neuropeptide release. This resistant component was dose dependently inhibited by SNX-482, with an IC₅₀ of 4.1 nM. Furthermore, SNX-482 did not affect the other Ca²⁺ current types in these CNS terminals. Like the N- and P/Q-type Ca²⁺ currents, this SNX-482-sensitive transient Ca²⁺ current is high-threshold activated and shows moderate steady-state inactivation. At the same concentrations, SNX-482 blocked the component of oxytocin, but not of vasopressin, release that was resistant to the other channel blockers, indicating a preferential role for this type of Ca²⁺ current in oxytocin release from neurohypophysial terminals. Our results suggest that an _1E or "R"-type Ca²⁺ channel exists in oxytocinergic nerve terminals and, thus, functions in controlling only oxytocin release from the rat neurohypophysis.

Key words: class E (_1E) Ca²⁺ channel; secretion; SNX-482; vasopressin; posterior pituitary; oxytocin

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19219235-07$05.00/0

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