Intracellular Na+ inhibits voltage-dependent N-type Ca2+ channels by a G protein betagamma subunit-dependent mechanism.
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.
Blumenstein
Yakov
Y
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. dascaln@post.tau.ac.il
Maximyuk
Olexandr P
OP
Lozovaya
Natalia
N
Yatsenko
Natalia M
NM
Kanevsky
Nataly
N
Krishtal
Oleg
O
Dascal
Nathan
N
D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism* / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D044388:GTP-Binding Protein gamma Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009865:Oocytes; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D014982:Xenopus laevis
D020864:Calcium Channels, N-Type; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D018377:Neurotransmitter Agents; D012964:Sodium; D019206:GTP-Binding Protein alpha Subunits, Gi-Go