Regulation of human neuronal calcium channels by G protein βγ subunits expressed in human embryonic kidney 293 cells

Lee R. Shekter, Ronald Taussig, Samantha E. Gillard, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


We examined the ability of different G protein subunits to inhibit the activity of human α1B and α1E Ca2+ channels stably expressed in human embryonic kidney (HEK) 293 cells together with β1B and α2Bδ Ca2+ channel subunits. Under normal conditions, Ca2+ currents in αlB-expressing cells showed little facilitation after a depolarizing prepulse. However, when we overexpressed the β2γ2 subunits of heterotrimeric G proteins, the time course of activation of the Ca2+ currents was considerably slowed and a depolarizing prepulse produced a large facilitation of the current as well as an acceleration in its time course of activation. Similar effects were not observed when cells were transfected with constitutively active mutants of the G protein α subunits αs, αi1, and αo or with the G protein β2 and γ2 subunits alone. Studies carried out in cells expressing α1E currents showed that overexpression of β2γ2 subunits produced prepulse facilitation, although this was of lesser magnitude than that observed with Ca2+ currents in α1B-expressing cells. The subunits β2 and γ2 alone produced no effects, nor did constitutively active αs, αi1, and αo subunits. Phorbol esters enhanced α1E Ca2+ currents but had no effect on α1B currents, suggesting that protein kinase C activation was not responsible for the observed effects. When α1E Ca2+ currents were expressed without their β subunits, they exhibited prepulse facilitation. These results demonstrate that α1E Ca2+ currents are less susceptible to direct modulation by G proteins than α1B currents and illustrate the antagonistic interactions between Ca2+ channel β subunits and G proteins.

Original languageEnglish (US)
Pages (from-to)282-291
Number of pages10
JournalMolecular pharmacology
Issue number2
StatePublished - Aug 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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