The Properties of Carbachol-Activated Nonselective Cation Channels at the Single Channel Level in Guinea Pig Gastric Myocytes

We investigated the properties of carbachol (CCh)-activated nonselective cation channels (NSC(CCh)) at the single channel level in the gastric myocytes of guinea pigs using a magnified whole-cell mode or an outside-out mode. The channel activity (NPo) recorded in a magnified whole-cell mode increased with depolarization (from -120 to -20 mV) and had the half activation potential of -81 mV under the symmetrical 140 mM Cs+ condition. The single channel conductance depended upon the extracellular monovalent cations with the order of Cs+ (35 pS) > Na+ (25 pS) > Li+ (21 pS). The channel activities markedly diminished or disappeared when external Cs+ was replaced with Na+ or N-methyl-D-glucamate (NMDG+). With Cs+ and Na+ as external cations, the channel showed a monotonic increase in NPo with the increased mole fraction of Cs+ over Na+, and it had an intermediate conductance value in solution containing 67% Cs+ with 33% Na+. These data suggested that the extracellular monovalent cations regulate the whole-cell current of NSC(CCh) by modulating both the open state probability and the unitary conductance, and there is one binding site for the extracellular cations within the pore.