Selective G-protein regulation of neuronal calcium channels

Peter T. Toth, Lee R. Shekter, Gloria Hui Ma, Louis H. Philipson, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

We examined the properties and regulation of Ca channels resulting from the expression of human α(1B) and α(1E) subunits stably expressed in HEK293 cells. The ancillary subunits β(1B) and α2/δ were also stably expressed in these cell lines. Ca currents in α(1B)-expressing cells had the properties of N-type currents. Ca currents in cells expressing α(1E) exhibited a novel profile that was similar to the properties of the 'R type' Ca current. Introduction of GTP-γ-S into α(1B) cells greatly enhanced the extent of prepulse facilitation of the Ca current, whereas it had only a very small effect in α(1E)-expressing cells. Activation of somatostatin receptors endogenous to HEK293 cells or κ opioid receptors, expressed in the cells after transfection, inhibited Ca currents in α(1B)-expressing cells. This inhibition was blocked by pertussis toxin and was partially relieved by a depolarizing prepulse. In contrast, no inhibitory effects were noted in cells expressing α(1E) channels under the same circumstances. HEK293 cells normally contained G-proteins from all of the four major families. Inhibition of Ca currents by κ agonists in α(1B)-expressing cells was enhanced slightly by the cotransfection of several G-protein α subunits. κ agonists, however, had no effect in α(1E)-containing cells, even after overexpression of different G-protein α-subunits. In summary, these results demonstrate that there is a large difference in the susceptibility of α(1B)- and α(1E)- based Ca channels to regulation by G-proteins. This is so despite the fact that the two types of Ca channels show substantial similarities in their primary sequences.

Original languageEnglish (US)
Pages (from-to)4617-4624
Number of pages8
JournalJournal of Neuroscience
Volume16
Issue number15
DOIs
StatePublished - Aug 1 1996

Keywords

  • Ca channel
  • G-protein
  • HEK293
  • patch clamp
  • somatostatin
  • κ receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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