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 ca tion channels (NSCCCh) at the single channel level in the gastric myocytes of guinea pigs using a magnified whole-cell mode or an outside-out mode. Th e channel activity (NPo) recorded in a magnified whole-cell mode increased with depolarization (from -120 to -20 mV) and had the half activation poten tial of -81 mV under the symmetrical 140 mM Cs+ condition. The single chann el conductance depended upon the extracellular monovalent cations with the order of Cs+ (35 pS) > Na+ (25 pS) > Li+ (21 pS). The channel activities ma rkedly 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 NP, 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 extracellula r monovalent cations regulate the whole-cell current of NSCCCh by modulatin g both the open state probability and the unitary conductance, and there is one binding site for the extracellular cations within the pore.