DIHYDROPYRIDINES AND VERAPAMIL INHIBIT VOLTAGE-DEPENDENT K-CELLS OF THE GUINEA-PIG( CURRENT IN ISOLATED OUTER HAIR)

Dihydropyridines and verapamil are widely used as blockers of voltage- dependent Ca++ channels. In this work we show that these compounds can have a direct blocking action on a class of voltage-activated potassi um channels. Voltage-dependent whole-cell currents were recorded from isolated guinea-pig outer hair cells (OHCs) under conditions such that the free Ca++ concentration in both the internal and external solutio ns was minimized. A substantial Ca++-independent K+ current was reveal ed by this procedure. Both conventional K+ and Ca++ channel ligands in hibited this current. The order of potency (in terms of the half inhib itory concentrations (IC50) of channel inhibitors) was: nimodipine (6 mu M) > Bay K 8644 (8 mu M) > verapamil (11 mu M)> 4-aminopyridine (22 mu M) > nifedipine (32 mu M) > quinine (49 mu M) > TEA (10236 mu M). Except for verapamil, these channel ligands reduced the size of the K currents without much alteration of the time course of the currents. In contrast, verapamil caused a more than 10-fold increase in the appa rent inactivation rate of the K+ currents without significantly alteri ng the activation of the currents. The observation that relatively low concentrations of calcium channel ligands can directly inhibit potass ium currents in isolated OHCs indicates that caution should be taken w hen these pharmacological agents are used as tools for studying cochle ar hair cell physiology.