학술논문
Intracellular Na+ inhibits voltage-dependent N-type Ca2+ channels by a G protein betagamma subunit-dependent mechanism.
Document Type
Academic Journal
Author
Blumenstein Y; Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. dascaln@post.tau.ac.il; Maximyuk OP; Lozovaya N; Yatsenko NM; Kanevsky N; Krishtal O; Dascal N
Source
Publisher: Cambridge Univ. Press Country of Publication: England NLM ID: 0266262 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0022-3751 (Print) Linking ISSN: 00223751 NLM ISO Abbreviation: J Physiol Subsets: MEDLINE
Subject
Language
English
ISSN
0022-3751
Abstract
N-type voltage-dependent Ca(2+) channels (N-VDCCs) play important roles in neurotransmitter release and certain postsynaptic phenomena. These channels are modulated by a number of intracellular factors, notably by Gbetagamma subunits of G proteins, which inhibit N-VDCCs in a voltage-dependent (VD) manner. Here we show that an increase in intracellular Na(+) concentration inhibits N-VDCCs in hippocampal pyramidal neurones and in Xenopus oocytes. In acutely dissociated hippocampal neurones, Ba(2+) current via N-VDCCs was inhibited by Na(+) influx caused by the activation of NMDA receptor channels. In Xenopus oocytes expressing N-VDCCs, Ba(2+) currents were inhibited by Na(+) influx and enhanced by depletion of Na(+), after incubation in a Na(+)-free extracellular solution. The Na(+)-induced inhibition was accompanied by the development of VD facilitation, a hallmark of a Gbetagamma-dependent process. Na(+)-induced regulation of N-VDCCs is Gbetagamma dependent, as suggested by the blocking of Na(+) effects by Gbetagamma scavengers and by excess Gbetagamma, and may be mediated by the Na(+)-induced dissociation of Galphabetagamma heterotrimers. N-VDCCs may be novel effectors of Na(+)ion, regulated by the Na(+) concentration via Gbetagamma.