Characterization of muscarinic receptor-mediated cationic currents in longitudinal smooth muscle cells of mouse small intestine.

In mouse intestinal smooth muscle cells held at -50 mV, carbachol evoked an atropine-sensitive inward current in the intracellular presence of Cs(+). The current response consisted of an initial peak followed by a smaller plateau component on which oscillatory currents frequently arose. Results from various experimental procedures indicated that the inward current is a muscarinic receptor-operated cationic current (mI(cat)) sensitive to cytosolic Ca(2+) concentration ([Ca(2+)](i)) and that the initial peak and oscillatory components are contaminated by Ca(2+)-activated Cl(-) currents. Under conditions of [Ca(2+)](i) buffered to 100 nM, the mI(cat) response to cumulative carbachol applications was inhibited competitively by an M(2)-selective antagonist but non-competitively by an M(3)-selective one. Also it was severely reduced by pertussis toxin (PTX) treatment or a phospholipase C (PLC) inhibitor. Comparative analysis of mI(cat) in mouse and guinea-pig intestinal myocytes indicated that the underlying channels resemble between those myocytes in agonist sensitivity, current-voltage relationship, and unitary conductance. The results suggest that in mouse intestinal myocytes, mI(cat) arises mainly via an M(2)/M(3) synergistic mechanism involving PTX-sensitive G-proteins and PLC activity in the absence of current modulation by [Ca(2+)](i) changes, as described for guinea-pig ileal mI(cat). The channels underlying mI(cat) are also indistinguishable in gating properties between both types of myocytes.