Potential synergy: voltage-driven steps in receptor-G protein coupling and beyond.

G protein-coupled receptor responses are not generally considered to show voltage dependence, but recently, the sensitivity of an oocyte to acetylcholine, which activates the m2 subtype of muscarinic receptors, was shown to be affected by changes in the membrane potential. Another example is the m2 receptor-evoked cation current in mammalian smooth muscle cells, which shows strong voltage dependence even when the receptor is bypassed by activating the G protein directly by intracellular application of GTPgammaS, a hydrolysis-resistant guanosine triphosphate (GTP) analog. Even among the few examples of voltage-dependent behavior known from among the plethora of G protein-coupled responses, the mechanism underlying the voltage dependence seems to differ.