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. 2011 Jan 26;589(Pt 7):1741–1753. doi: 10.1113/jphysiol.2010.204107

Figure 7. Mutations in residues forming the putative ligand binding pocket alter the voltage dependence of M2R gating charge displacement.

Figure 7

A, QON–V relationships for M2R mutants heterologously expressed in oocytes. Red line denotes WT M2R QON–V relationship. B, concentration–response for IKACh activation in HEK-293 cells heterologously expressing WT or mutant M2R and Kir3.1/3.4 channels. Concentration–response curves for WT M2R-mediated IKACh activation at Vh−100 mV (open squares) and +50 mV (open circles). The EC50 and Hill coefficient were 14 ± 3 nm and 0.8 ± 0.1 (Vh−100 mV) and 62 ± 6 nm and 0.9 ± 0.1 (Vh+50 mV). Concentration–response curves for W99A M2R-mediated IKACh activation at Vh−100 mV (hatched squares) and +30 mV (hatched circles). The EC50 and Hill coefficient were 3.0 ± 0.4 μm and 0.8 ± 0.1 (Vh−100 mV) and 3.2 ± 0.5 μm and 0.9 ± 0.1 (Vh+30 mV). Data points represent mean ± SEM of 4–8 cells. C, the potency of S107 M2R for ACh varies with membrane voltage. Concentration–response curves for S107A M2R-mediated IKACh activation in HEK-293 cells heterologously expressing S107A mutant M2R and Kir3.1/3.4 channels at Vh−100 mV (squares) and +50 mV (circles). The EC50 and Hill coefficient were 5.4 ± 1.0 μm and 0.7 ± 0.2 (Vh−100 mV) and 20.6 ± 4.6 μm and 0.7 ± 0.2 (Vh+50 mV). Data points represent mean ± SEM of 4–7 cells.