An R-type Ca(2+) current in neurohypophysial terminals preferentially regulates oxytocin secretion.
Multiple types of voltage-dependent Ca(2+) 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 Ca(2+) channels in neuropeptide release have been identified previously (Wang et al., 1997a). Although the L- and N-type Ca(2+) currents play equivalent roles in both vasopressin and oxytocin release, the P/Q-type Ca(2+) current only regulates vasopressin release. An oxytocin-release and Ca(2+) current component is resistant to the L-, N-, and P/Q-type Ca(2+) channel blockers but is inhibited by Ni(2+). A new polypeptide toxin, SNX-482, which is a specific alpha(1E)-type Ca(2+) channel blocker (Newcomb et al., 1998), was used to characterize the biophysical properties of this resistant Ca(2+) current component and its role in neuropeptide release. This resistant component was dose dependently inhibited by SNX-482, with an IC(50) of 4.1 nM. Furthermore, SNX-482 did not affect the other Ca(2+) current types in these CNS terminals. Like the N- and P/Q-type Ca(2+) currents, this SNX-482-sensitive transient Ca(2+) 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 Ca(2+) current in oxytocin release from neurohypophysial terminals. Our results suggest that an alpha(1E) or "R"-type Ca(2+) channel exists in oxytocinergic nerve terminals and, thus, functions in controlling only oxytocin release from the rat neurohypophysis.
Wang
G
G
Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Dayanithi
G
G
Newcomb
R
R
Lemos
J R
JR
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020908:Calcium Channels, R-Type / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D020908:Calcium Channels, R-Type; D010455:Peptides; C115521:SNX 482; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D001127:Arginine Vasopressin; D010121:Oxytocin; C078452:ziconotide; D009529:Nicardipine