Blockade of bepridil on I(A) and I(K) in acutely hippocampal CA1 neurons

The effects of bepridil, an antianginal agent with antiarrhythmic action, on voltage-dependent K⁺ currents in the CA1 pyramidal neurons acutely isolated from rat hippocampus were studied by means of whole-cell patch clamp techniques. Current recordings were made in the presence of TTX to block Na⁺ current. Depolarizing test pulses activated two components of outward K⁺ currents: a rapidly activating and inactivating component, I(A); and a delayed component, I(K). Results showed that bepridil reduced the amplitude of I(A) and I(K), and exerted its inhibitory action in time- and dose-dependent manner. Half-blocking concentrations (IC₅₀) of bepridil on I(A) and I(K) were 17.8 μM and 1.7 μM, respectively. 10 μM 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 μM bepridil inhibited I(K) by 71.6% at +30 mV of depolarization; 10 μM bepridil positively shifted the voltage-dependent of activation curves of I(A) and I(K) 12.1 mV and 28.7 mV, respectively. These results suggested that blockade on K⁺ currents by bepridil is preferential for I(K), and contributes to the protection brain against ischemic damage.