Activating effect of the flavonoid phloretin on Ca(2+)-activated K+ channels in myelinated nerve fibers of Xenopus laevis [corrected].

The effects of the flavonoid phloretin on K+ channels in amphibian myelinated nerve were studied by patch clamping. The open probability of Ca(2+)-activated K+ channels was greatly increased by external phloretin (10-200 microM) due to a shift of the membrane potential for half-maximal activation, E50, of -63.9 mV (80 microM phloretin). Open times were prolonged and closed times shortened. Channel activation by phloretin developed slowly (tau on = 33.4 s) and its washout was even slower (tau off,1 = 4.7 and tau off,2 = 183.2 s). In contrast, submillimolar phloretin blocked two delayed rectifier K+ channels (I and F) whereas the gating of the ATP-sensitive and the flickering K+ channel were unaffected. Phloretin may directly affect the voltage sensor of K+ channels.