Caffeine rapidly decreases potassium conductance of dissociated outer hair cells of guinea-pig cochlea

The effects of caffeine on the outer hair cells (OHCs) freshly dissociated from guinea-pig cochlea were investigated with the whole-cell patch-clamp technique, in both the conventional and the nystatin perforated patch-clamp configurations under voltage-clamp condition. Application of caffeine (> 1 mM for 10–30 s) induced an inward current (I_caffeine) with decrease of conductance in a dose-dependent manner at a holding potential (V_H) of −60 mV. The reversal potential ofI_caffeine (E_caffeine) was close to the K⁺ equilibrium potential. TheI_caffeine was not affected by Ca²⁺-free external solution. The internal perfusion of the Ca²⁺ chelator BAPTA had no effect onI_caffeine. TheI_caffeine was not modulated by the external application of H-8 or staurosporine and by the internal perfusion of GDP-βS. The amplitude ofI_caffeine was the largest at the basal region of OHCs when caffeine was locally applied by the ‘puffer’ method. These results suggest that caffeine induces a decrease in membrane potassium conductance of the OHCs mainly at the basal region without mediating the intracellular signaling pathway.