Department of Physiology
Animals; Arginine Vasopressin; Calcium Channel Blockers; Calcium Channels, R-Type; Membrane Potentials; Nerve Endings; Nicardipine; Oxytocin; Patch-Clamp Techniques; Peptides; Pituitary Gland, Posterior; Rats; Spider Venoms; omega-Agatoxin IVA; *omega-Conotoxins
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Neurosci. 1999 Nov 1;19(21):9235-41.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Wang, Gang; Dayanithi, Govindan; Newcomb, Robert; and Lemos, Jose R., "An R-type Ca(2+) current in neurohypophysial terminals preferentially regulates oxytocin secretion" (1999). Open Access Articles. 1177.