M2 and M3 muscarinic receptors couple, respectively, with activation of nonselective cationic channels and potassium channels in intestinal smooth muscle cells.

Smooth muscle cells of guinea pig ileum express both M2 and M3 subtypes of muscarinic receptors. Under voltage clamp, activation of the muscarinic receptors with carbachol (CCh) induces Ca2+-activated K+ current (I[K-Ca]) and nonselective cationic current (Icat). Receptor subtypes mediating the current responses were characterized by using pirenzepine, AF-DX116, 4-DAMP and atropine, which have different profiles of the affinity constants for muscarinic receptor subtypes. The muscarinic antagonists inhibited either CCh-evoked I(K-Ca) or Icat with different potencies. Their relative potencies for I(K-Ca) and Icat inhibition resembled the relative affinity constants for M3 and M2 subtypes, respectively. Thus, the I(K-Ca) is mediated via the M3 subtype and the Icat via the M2 subtype.