Regulation of CaV2 calcium channels by G protein coupled receptors

• Published in: Biochimica et biophysica acta 2013-07, Vol.1828 (7), p.1629-1643
• Main Authors: Zamponi, Gerald W., Currie, Kevin P.M.
• Format: Article
• Language: English
• Subjects: Arachidonic acid; Calcium channel; G protein coupled receptor; Gβγ; PiP2; Tyrosine kinase
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2012.10.004

Voltage gated calcium channels (Ca2+ channels) are key mediators of depolarization induced calcium influx into excitable cells, and thereby play pivotal roles in a wide array of physiological responses. This review focuses on the inhibition of CaV2 (N- and P/Q-type) Ca2+-channels by G protein coupled receptors (GPCRs), which exerts important autocrine/paracrine control over synaptic transmission and neuroendocrine secretion. Voltage-dependent inhibition is the most widespread mechanism, and involves direct binding of the G protein βγ dimer (Gβγ) to the α1 subunit of CaV2 channels. GPCRs can also recruit several other distinct mechanisms including phosphorylation, lipid signaling pathways, and channel trafficking that result in voltage-independent inhibition. Current knowledge of Gβγ-mediated inhibition is reviewed, including the molecular interactions involved, determinants of voltage-dependence, and crosstalk with other cell signaling pathways. A summary of recent developments in understanding the voltage-independent mechanisms prominent in sympathetic and sensory neurons is also included. This article is part of a Special Issue entitled: Calcium channels. [Display omitted] ► CaV2 channels play pivotal roles in neurotransmitter and hormone release. ► G protein coupled receptors orchestrate precise control of CaV2 channels. ► Voltage-dependent inhibition is mediated by direct binding of Gβγ to the channels. ► Voltage-independent inhibition is mediated by several other distinct pathways. ► Current understanding of these important mechanisms is provided in this review.