In rat paraventricular thalamic nucleus (PVT) neurons, activation of thyrotropin releasing hormone (TRH) receptors enhances neuronal excitability via concurrent decrease in a GIRK-like conductance and opening of a cannabinoid receptor-sensitive transient receptor potential canonical (TRPC)-like conductance. Here we investigated the calcium (Ca2+) 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 [Ca2+]o, suggesting a critical role for both intracellular Ca2+ release and Ca2+ influx. TRH-induced inward current was unchanged by T-type Ca2+ channel blockade, but was decreased by blockade of high-voltage-activated Ca2+ 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 Ca2+ influx via L-type Ca2+ channels. Only the TRPC-like conductance was reduced by either thapsigargin or dantrolene, suggesting a role for ryanodine receptors and Ca2+-induced Ca2+ release (CICR) in this component of the TRH-induced response. In pituitary and other cell lines, TRH stimulates mitogen activated protein kinase (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 Ca2+ influx via opening of L-type Ca2+ channels, a sensitivity of a TRPC-like component to intracellular Ca2+ release via ryanodine channels, and a modulation by MAPK of a GIRK-like conductance component.
- Thyrotropin releasing hormone
- thalamic paraventricular neurons
- mitogen -activated protein kinase
- -type Ca2+ channels
- TRPC-like and GIRK-like currents
- Copyright © 2016, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology