BLOCKADE OF BEPRIDIL ON I-A AND I-K IN ACUTELY ISOLATED HIPPOCAMPAL CA1 NEURONS

The effects of bepridil, an antianginal agent with antiarrhythmic acti on, on voltage-dependent K+ currents in the CA1 pyramidal neurons acut ely isolated from rat hippocampus were studied by means of whole-cell patch clamp techniques. Current recordings were made in the presence o f TTX to block Na+ current. Depolarizing test pulses activated two com ponents of outward K+ currents: a rapidly activating and inactivating component, I-A; and a delayed component, I-K. Results showed that bepr idil reduced the amplitude of I, and I-K, and exerted its inhibitory a ction in time- and dose-dependent manner. Half-blocking concentrations (IC50) of bepridil on I-A and I-K were 17.8 mu M and 1.7 mu M, respec tively. 10 mu M bepridil suppressed I-A and I-K by 46.7% and 77.1% at +30 mV of depolarization, respectively. When I-K was activated nearly uncontaminated with I-A by holding at -50 mV, 10 mu M bepridil inhibit ed I-K by 71.6% at +30 mV of depolarization; 10 mu M bepridil positive ly shifted the voltage-dependent of activation curves of I-A and I-K 1 2.1 mV and 28.7 mV, respectively. These results suggested that blockad e on K+ currents by bepridil is preferential for I-K, and contributes to the protection brain against ischemic damage. (C) 1998 Elsevier Sci ence B.V. All rights reserved.