title: Patch-clamp analysis of the mechanism of PACAP-induced excitation in rat supraoptic neurones.
abstract: In neurosecretory cells of the supraoptic nucleus (SON) of rats, pituitary adenylate cyclase activating polypeptide (PACAP) causes an increase in [Ca2+]i, and stimulates somatodendritic vasopressin (VP) release. In this report, to elucidate the ionic mechanism of the action of PACAP, membrane potentials and ionic currents were measured from SON neurones in slice preparations or from dissociated SON neurones. In the current clamp mode, PACAP depolarized membrane potentials of both phasic and non-phasic neurones and increased the firing rate. Moreover, simultaneous measurements of membrane potentials and [Ca2+]i revealed that the membrane depolarization correlated well with increases in [Ca2+]i. In the voltage-clamp mode, PACAP induced inward currents at a holding potential of -70 or -80 mV in a dose-dependent manner and the time course of the currents was similar to that of the PACAP-induced membrane depolarization. The averaged reversal potential of the PACAP-induced currents obtained from dissociated SON neurones was -33 mV, which was close to the reversal potential of non-selective cation currents in SON neurones. The currents were rapidly and reversibly inhibited by a cation-channel blocker, gadolinium. Analysis of synaptic inputs into SON neurones in slice preparations revealed that PACAP had little or no effects on the frequency of spontaneous excitatory and inhibitory postsynaptic currents. These results suggest that pituitary adenylate cyclase activating polypeptide (PACAP) activates PACAP receptors in the postsynaptic membrane of the supraoptic nucleus (SON) neurones, and that the activation of PACAP receptors leads to opening of non-selective cation channels, depolarization of the membrane potential, and increase in the firing rate in SON neurones. Such mechanisms may account for the PACAP-induced increase in [Ca2+]i and vasopressin (VP) release observed in SON neurones.
authors.affiliation: Department of Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan. shibuya@med.uoeh-u.ac.jp
authors.forename: I
authors.initials: I
authors.lastname: Shibuya
authors.forename: N
authors.initials: N
authors.lastname: Kabashima
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: V S
authors.initials: VS
authors.lastname: Setiadji
authors.forename: J
authors.initials: J
authors.lastname: Noguchi
authors.forename: N
authors.initials: N
authors.lastname: Harayama
authors.forename: Y
authors.initials: Y
authors.lastname: Ueta
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010902:Pituitary Gland / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000262:Adenylyl Cyclases; D002118:Calcium