Regulation of Cl- conductance in delayed shortening and shrinkage of outer hair cells.

Abstract

Tetanic electrical field stimulation induces slow and delayed shortening of isolated outer hair cells (OHCs) from guinea pigs concomitant with a decrease in cell volume and intracellular Cl- concentration ([Cl-]i). These responses are dependent on the entry of Ca2+ and the activation of both Ca(2+)-activated K+ channels and furosemide-sensitive Cl- channels. In this study, the regulatory mechanisms of the Cl- channels of OHCs were investigated. Tetanic stimulation induced shrinkage and a decrease in [Cl-]i, the latter being unrelated to the activity of the Na+/K+/2Cl- cotransporter. These responses were inhibited by tetraethylammonium, and the inhibition was overcome by an increase in the K+ conductance by valinomycin, though valinomycin alone did not affect the resting cell volume and [Cl-]i. The deprivation of extracellular Ca2+ inhibited the stimulation-induced changes in volume and [Cl-]i even in the presence of valinomycin. These results suggest that electrical stimulation-induced delayed shortening and shrinkage of OHCs are induced by Cl- efflux, which is electrically coupled to K+ efflux and independently activated following an increase in intracellular Ca2+ concentration.