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 (Icaffeine) with decrease of conductance in a dose-dependent manner at a holding potential (VH) of -60 mV. The reversal potential of Icaffeine (Ecaffeine) was close to the K+ equilibrium potential. The Icaffeine was not affected by Ca(2+)-free external solution. The internal perfusion of the Ca2+ chelator BAPTA had no effect on Icaffeine. The Icaffeine was not modulated by the external application of H-8 or staurosporine and by the internal perfusion of GDP-beta S. The amplitude of Icaffeine 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.