G protein coupled receptors (GPCRs) participate in the majority of signal transduction processes in the body. Specifically, the binding of an external agonist promotes coupling of the GPCR to its G protein and this, in turn, induces downstream signaling. Recently, it was shown that agonist binding to the M2 muscarinic receptor (M2R) and to other GPCRs is voltage dependent. Here we examine, whether the coupling of the M2R to its G protein is also voltage-dependent. We first show, in Xenopus oocytes, that the activity of the M2R in the absence of agonist (constitutive activity) can be used to report the coupling. We then show that the coupling is, by itself, voltage dependent. This novel finding is of physiological importance, as it shows that the actual signal transduction, whose first step is the coupling of the GPCR to its cognate G protein, is voltage dependent.
Bibliographical noteFunding Information:
This work was supported by the Israel Science Foundation grant no. 606-15 to YBC and HP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2019 Ben-Chaim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.