NEUROPEPTIDE Y-1 RECEPTORS INHIBIT N-TYPE CALCIUM CURRENTS AND REDUCETRANSIENT CALCIUM INCREASES IN RAT DENTATE GRANULE CELLS

Neuropeptide Y (NPY) is far more abundant in the dentate gyrus than el sewhere in the hippocampal formation, but it does not alter the synapt ic excitation of dentate granule cells (DGCs) as it does for pyramidal cells in areas CA1 and CA3. NPY inhibited depolarization-induced incr eases in intracellular Ca2+ concentrations ([Ca2+](i)) in DGCs in hipp ocampal slices, without altering the resting [Ca2+](i). NPY inhibited Ca2+ currents (I-Ca) via a Y-1 receptor in 84% of acutely isolated DGC s and via a Y-2 receptor in 31% of the NPY-responsive cells tested. I- Ca inhibition was completely occluded by omega-conotoxin-GVIA but not by nimodipine. The inhibition of I-Ca was accompanied by a change in t he lime course of I-Ca activation in only 27% of NPY-responsive cells. Only 23% of DGCs responded to NPY when Ba2+ was substituted for extra cellular Ca2+ and when [Ca2+](i) was strongly buffered. Therefore, NPY inhibits an N-type I-Ca in DGCs, mainly via Y-1 receptors. Furthermor e, it seems that more than one mechanism, one of which may be sensitiv e to [Ca2+](i), may couple NPY receptors to the Ca2+ channels in DGCs. Because the release of dynorphin from DGCs depends in part on N-type currents, NPY receptors are poised to regulate the release of opioid p eptides from DGC somata and dendrites.