Acetylcholine response in guinea pig outer hair cells. II. Activation of a small conductance Ca(2+)-activated K+ channel.

The type of K+ channel involved in the acetylcholine (ACh) evoked response (Ksub; sub stands for suberyldicholine) in guinea pig outer hair cells (OHCs) is still uncertain. The present study tests the hypotheses that Ksub is one of the following: a big conductance Ca(2+)-dependent K+ channel (BK), a small conductance Ca(2+)-dependent K+ channel (SK), a KA type of K+ channel, or a Kn type of K+ channel. Patch-clamp technique in the whole-cell mode was used to record from single guinea pig OHCs. ACh (100 microM) was applied to voltage-clamped OHCs and the ACh-induced currents (IACh) were measured. Charybdotoxin (100 nM) had no effect on IACh, while apamin (1 microM) blocked more than 90% of IACh. Lowering the external Ca2+ concentration caused a hyperpolarizing shift of the IACh monitored as a function of the prepulse voltage. Increasing internal Mg2+ (Mgi2+) concentration caused a reduction in the outward IACh without affecting the inward IACh. The Ksub channel was found to be permeable to Cs+. In Cs+ solutions, IACh was 45% of the IACh in K+ solutions. The block of IACh by apamin, the dependence on extracellular Ca2+, the incomplete block of IACh by Cs+, and the ACh-induced Cs+ currents favor the hypothesis that Ksub belongs to the SK type of channels. An ionotropic/nicotinic nature of the ACh mechanism of action is favored. It is suggested that, in vivo, the amplitude of the ACh-induced hyperpolarization may depend on the Ca2+/Mg2+ ratio inside and outside the cell.