M2 receptor stimulation results in the gating of nonselective cation channels in several smooth muscle cell types. However the requirement for current activation includes a rise in cytosolic calcium mediated by M3 receptor induced calcium release. This complex signaling system confers substantial complexity on the interpretation of pharmacological experiments. M2 and M3 receptor stimulation has also been linked to the inhibition of potassium channels in smooth muscle. These signaling events are likely to play important roles in excitation/contraction coupling.