Role of Multiple Voltage-Sensitive Calcium Channels in Depolarization-Induced Release of Neuropeptide Y and Luteinizing Hormone-Releasing Hormone from Rat Median Eminence-Arcuate Nucleus

Abstract

The objective of the present studies was to identify the subtypes of voltage-sensitive Ca2+ channels (VSCC) that regulate the basal and depolarization-induced release of neuropeptide Y (NPY) and LH-releasing hormone (LHRH) from rat hypothalamus. Tissues containing median eminence-arcuate nucleus (ME-ARC) were dissected from male rats and incubated in vitro in the presence and absence of agents selectively affecting N- or L-type VSCC. KCl depolarization-induced release of NPY, but not basal release, was abolished by Ca2+-free/EGTA medium and was significantly reduced by cobalt. The depolarization-induced release of both NPY and LHRH from ME-ARC was significantly augmented by BAY K 8644, an agonist at L-type VSCC, and this effect was blocked by nitrendipine, an antagonist at these channels. Neither agent modified basal release of NPY or LHRH. Nitrendipine alone blocked the release of NPY and LHRH evoked by a low concentration (23 mM) of KCl, but not by a higher concentration (45 mM). Omega-conotoxin (CgTX), which primarily blocks N-type VSCC, significantly blunted, but did not abolish, depolarization-induced release of NPY and LHRH without altering basal release. These findings suggest that multiple VSCC subtypes participate in the regulation of depolarization-induced release of NPY and LHRH. Similar to other systems, the N-type channel may be predominantly involved in the process by which entry of extracellular Ca2+ triggered by depolarization leads to the release of these two peptides. The inability of nitrendipine and CgTX to completely block depolarization-induced NPY and LHRH release suggests the involvement of at least one other VSCC in this process. Although L-type VSCC may not be of primary importance in depolarization-induced release of NPY and LHRH, activation of this channel subtype may enhance Ca2+ entry and therefore modulate release of these neuropeptides.