M2 AND M3-MUSCARINIC-RECEPTORS COUPLE, RESPECTIVELY, WITH ACTIVATION OF NONSELECTIVE CATIONIC CHANNELS AND POTASSIUM CHANNELS IN INTESTINALSMOOTH-MUSCLE CELLS

Smooth muscle cells of guinea pig ileum express both M2 and M3 subtype s of muscarinic receptors. Under voltage clamp, activation of the musc arinic receptors with carbachol (CCh) induces Ca2+-activated K+ curren t (IK-Ca) and nonselective cationic current (I-cat). Receptor subtypes mediating the current responses were characterized by using pirenzepi ne, AF-DX116, 4-DAMP and atropine, which have different profiles of th e affinity constants for muscarinic receptor subtypes. The muscarinic antagonists inhibited either CCh-evoked IK-Ca or I-cat with different potencies. Their relative potencies for IK-Ca and I-cat inhibition res embled the relative affinity constants for M3 and M2 subtypes, respect ively. Thus, the IK-Ca is mediated via the M3 subtype and the I-cat vi a the M2 subtype.