Activation of GPCRs modulates quantal size in chromaffin cells through Gβγ and PKC

Xiao Ke Chen, Lie Cheng Wang, Yang Zhou, Qian Cai, Murali Prakriya, Kai Lai Duan, Zu Hang Sheng, Christopher Lingle, Zhuan Zhou*

*Corresponding author for this work

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Exocytosis proceeds by either full fusion or 'kiss-and-run' between vesicle and plasma membrane. Switching between these two modes permits the cell to regulate the kinetics and amount of secretion. Here we show that ATP receptor activation reduces secretion downstream from cytosolic Ca2+ elevation in rat adrenal chromaffin cells. This reduction is mediated by activation of a pertussis toxin-sensitive Gi/o protein, leading to activation of Gβγ subunits, which promote the 'kiss-and-run' mode by reducing the total open time of the fusion pore during a vesicle fusion event. Furthermore, parallel activation of the muscarinic acetylcholine receptor removes the inhibitory effects of ATP on secretion. This is mediated by a G q pathway through protein kinase C activation. The inhibitory effects of ATP and its reversal by protein kinase C activation are also shared by opioids and somatostatin. Thus, a variety of G protein pathways exist to modulate Ca2+-evoked secretion at specific steps in fusion pore formation.

Original languageEnglish (US)
Pages (from-to)1160-1168
Number of pages9
JournalNature neuroscience
Volume8
Issue number9
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chen, X. K., Wang, L. C., Zhou, Y., Cai, Q., Prakriya, M., Duan, K. L., Sheng, Z. H., Lingle, C., & Zhou, Z. (2005). Activation of GPCRs modulates quantal size in chromaffin cells through Gβγ and PKC. Nature neuroscience, 8(9), 1160-1168. https://doi.org/10.1038/nn1529