Acetylcholine activates a K+ conductance permeable to Cs+ in guinea pig outer hair cells

Acetylcholine (ACh), the major neurotransmitter released by efferent nerve fibers in the cochlea, has been shown to activate a Ca(2+)-dependent K+ conductance in outer hair cells (OHCs). Previously we reported that this ACh operated conductance is permeable to Cs+. The purpose of the present study was to characterize further this Cs(+)-permeable channel and its dependency on Ca2+ using isolated OHCs and the patch clamp technique in the whole cell configuration. The changes in the ACh response were examined when Cs+, Ba2+, Cd2+, N-methyl-D-glucamine (NMG+) and tetraethylammonium (TEA+) were placed in the external or internal solutions. Cs+ substituted for K+ in carrying the ACh-evoked Ca(2+)-dependent K+ current. When NMG+/TEA+ was substituted for internal K+ ACh-evoked an inward and an outward current, and Cs+ substituted for external K+ blocked the outward but not the inward current evoked by ACh suggesting it was carried by K+. In the NMG+/TEA+ condition, when the cell was held at different Vh values for an extended period of time, the ACh-induced K+ current rectified. In Ba2+ (3 mM) with zero Ca2+ ACh failed to induce any detectable current and the ACh response slowly recovered from the Ba2+ block, suggesting a block at an intracellular site. Cd2+ (1 mM) readily and reversibly blocked ACh-induced currents even when carried by Cs+. This data suggests that ACh opens a channel selective for K+, conductive to Cs+ and dependent on Ca2+.