title: L-type calcium channels and MAP kinase contribute to thyrotropin-releasing hormone-induced depolarization in thalamic paraventricular nucleus neurons.
abstract: In rat paraventricular thalamic nucleus (PVT) neurons, activation of thyrotropin-releasing hormone (TRH) receptors enhances neuronal excitability via concurrent decrease in a G protein-coupled inwardly rectifying K (GIRK)-like conductance and opening of a cannabinoid receptor-sensitive transient receptor potential canonical (TRPC)-like conductance. Here, we investigated the calcium (Ca(2+)) contribution to the components of this TRH-induced response. TRH-induced membrane depolarization was reduced in the presence of intracellular BAPTA, also in media containing nominally zero [Ca(2+)]o, suggesting a critical role for both intracellular Ca(2+) release and Ca(2+) influx. TRH-induced inward current was unchanged by T-type Ca(2+) channel blockade, but was decreased by blockade of high-voltage-activated Ca(2+) channels (HVACCs). Both the pharmacologically isolated GIRK-like and the TRPC-like components of the TRH-induced response were decreased by nifedipine and increased by BayK8644, implying Ca(2+) influx via L-type Ca(2+) channels. Only the TRPC-like conductance was reduced by either thapsigargin or dantrolene, suggesting a role for ryanodine receptors and Ca(2+)-induced Ca(2+) release in this component of the TRH-induced response. In pituitary and other cell lines, TRH stimulates MAPK. In PVT neurons, only the GIRK-like component of the TRH-induced current was selectively decreased in the presence of PD98059, a MAPK inhibitor. Collectively, the data imply that TRH-induced depolarization and inward current in PVT neurons involve both a dependency on extracellular Ca(2+) influx via opening of L-type Ca(2+) channels, a sensitivity of a TRPC-like component to intracellular Ca(2+) release via ryanodine channels, and a modulation by MAPK of a GIRK-like conductance component.
authors.affiliation: Ottawa Hospital Research Institute, Neuroscience Program and University of Ottawa, Department of Medicine, Ottawa, Ontario, Canada.
authors.forename: Miloslav
authors.initials: M
authors.lastname: Kolaj
authors.affiliation: Ottawa Hospital Research Institute, Neuroscience Program and University of Ottawa, Department of Medicine, Ottawa, Ontario, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Ottawa Hospital Research Institute, Neuroscience Program and University of Ottawa, Department of Medicine, Ottawa, Ontario, Canada lprenaud@ohri.ca.
authors.forename: Leo P
authors.initials: LP
authors.lastname: Renaud
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D020644:Midline Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage*
chemical_list: D020746:Calcium Channels, L-Type; D013973:Thyrotropin-Releasing Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium
keywords: L-type Ca2+ channels; TRPC-like and GIRK-like currents; mitogen-activated protein kinase; thalamic paraventricular neurons; thyrotropin-releasing hormone