Characterization of Muscarinic Receptor-Mediated Cationic Currents in Longitudinal Smooth Muscle Cells of Mouse Small Intestine

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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 Ca²⁺ concentration ([Ca²⁺]_i) and that the initial peak and oscillatory components are contaminated by Ca²⁺-activated Cl⁻ currents. Under conditions of [Ca²⁺]_i buffered to 100 nM, the mI_cat response to cumulative carbachol applications was inhibited competitively by an M₂-selective antagonist but non-competitively by an M₃-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 M₂/M₃ synergistic mechanism involving PTX-sensitive G-proteins and PLC activity in the absence of current modulation by [Ca²⁺]_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.