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

Abstract

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 (NP_o) 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 NP_o 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.