Multiple neuropeptide Y receptors regulate K+ and Ca2+ channels in acutelyisolated neurons from the rat arcuate nucleus

We examined the effects of neuropeptide Y (NPY) and related peptides on Ca2 + and K+ currents in acutely isolated neurons from the arcuate nucleus of t he rat. NPY analogues that activated all of the known NPY receptors (YI-E'S ), produced voltage-dependent inhibition of Ca2+ currents and activation of inwardly rectifying K+ currents in arcuate neurons. Both of these effects could occur simultaneously in the same cells. In some cells, activation of Y4 NPY receptors also caused oscillations in [Ca2+](i). NPY hyperpolarized arcuate neurons through the activation of a K+ conductance and increased th e spike threshold. Molecular biological studies indicated that arcuate neur ons possessed all of the previously cloned NPY receptor types (Y1, Y2, Y4. and Y5). Thus activation of multiple types NPY receptors on arcuate neurons can regulate both Ca2+ and K+ conductances leading to a reduction in neuro nal excitability and a suppression of neurotransmitter release.