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Sci. STKE, 24 June 2003
Vol. 2003, Issue 188, p. tw235
[DOI: 10.1126/stke.2003.188.tw235]


RECEPTORS Voltage-Sensitive GPCRs

Changes in membrane potential contribute to many cellular processes. Voltage-gated ion channels are the plasma membrane proteins most often considered to be the proteins responsive to changes in membrane potential. However, Ben-Chaim et al. pursued some previous observations suggesting that muscarinic acetylcholine receptor mAchR responses are voltage-sensitive. RNAs for muscarinic type 1 (m1R) or type 2 (m2R) receptors, along with necessary downstream effectors, were injected into Xenopus oocytes. The authors showed that the m2R responses and acetylcholine (ACh) binding were decreased at depolarized potentials. In contrast, m1R responses and ACh binding were increased at depolarized potentials. Thus, the difference in response and binding were not the consequence of charge repulsion due to positive membrane potentials decreasing the ability of the positively charged ACh to access the receptors. In oocytes treated with pertussis toxin to decrease m2R coupling to the G protein, binding of ACh was decreased at all potentials and concentrations of ACh compared with those of untreated oocytes. Therefore, the authors propose that membrane potential influences G protein-receptor coupling, such that for example, at resting membrane potentials, m2R and its cognate G protein are associated, which maintains the receptor in its high-affinity state.

Y. Ben-Chaim, O. Tour, N. Dascal, I. Parnas, H. Parnas, The M2 muscarinic G-protein-coupled receptor is voltage-sensitive. J. Biol. Chem. 278, 22482-22491 (2003). [Abstract] [Full Text]

Citation: Voltage-Sensitive GPCRs. Sci. STKE 2003, tw235 (2003).

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