G protein βγ subunits modulate the number and nature of exocytotic fusion events in adrenal chromaffin cells independent of calcium entry

Eun Ja Yoon, Heidi E. Hamm, Kevin P.M. Currie

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

G-protein-coupled receptors (GPCR) play important roles in controlling neurotransmitter and hormone release. Inhibition of voltage-gated Ca 2+ channels (Ca2+ channels) by G protein βγ subunits (Gβγ) is one prominent mechanism, but there is evidence for additional effects distinct from those on calcium entry. However, relatively few studies have investigated the Ca2+-channel-independent effects of Gβγ on transmitter release, so the impact of this mechanism remains unclear. We used carbon fiber amperometry to analyze catecholamine release from individual vesicles in bovine adrenal chromaffin cells, a widely used neurosecretory model. To bypass the effects of Gβγ on Ca2+ entry, we stimulated secretion using ionomycin (a Ca2+ ionophore) or direct intracellular application of Ca2+ through a patch pipette. Activation of endogenous GPCR or transient transfection with exogenous Gβγ significantly reduced the number of amperometric spikes (the number of vesicular fusion events). The charge ("quantal size") and amplitude of the amperometric spikes were also significantly reduced by GPCR/Gβγ. We conclude that independent from effects on calcium entry, Gβγ can regulate both the number of vesicles that undergo exocytosis and the amount of catecholamine released per fusion event. We discuss possible mechanisms by which Gβγ might exert these novel effects including interaction with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex.

Original languageEnglish (US)
Pages (from-to)2929-2939
Number of pages11
JournalJournal of Neurophysiology
Volume100
Issue number5
DOIs
StatePublished - Nov 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

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