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

Xiao-Ke Chen^1, 6, Lie-Cheng Wang^1, 6, Yang Zhou^1, 2, Qian Cai³, Murali Prakriya⁴, Kai-Lai Duan^1, 2, Zu-Hang Sheng³, Christopher Lingle⁴ & Zhuan Zhou^1, 2, 5

¹  Institute of Neuroscience, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences, Shanghai 200031, China.

²  Institute of Molecular Medicine, Peking University, Beijing 100871, China.

³  Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.

⁴  Department of Anesthesiology, Washington University, St. Louis, Missouri 63110, USA.

⁵  State Key Laboratory of Biomembrane Engineering, College of Life Sciences, Peking University, Beijing 100871, China.

⁶  These authors contributed equally to this work.

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 G_i/o protein, leading to activation of G 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.

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