Blockade of bepridil on IA and IK in acutely isolated 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, IA; and a delayed component, IK. Results showed that bepridil reduced the amplitude of IA and IK, and exerted its inhibitory action in time- and dose-dependent manner. Half-blocking concentrations (IC50) of bepridil on IA and IK were 17.8 microM and 1.7 microM, respectively. 10 microM bepridil suppressed IA and IK by 46.7% and 77.1% at +30 mV of depolarization, respectively. When IK was activated nearly uncontaminated with IA by holding at -50 mV, 10 microM bepridil inhibited IK by 71.6% at +30 mV of depolarization; 10 microM bepridil positively shifted the voltage-dependent of activation curves of IA and IK 12.1 mV and 28.7 mV, respectively. These results suggested that blockade on K+ currents by bepridil is preferential for IK, and contributes to the protection brain against ischemic damage.
Hu
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H
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China. yihuco@public1.ptt.js.cn
Yang
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D
Lin
Z
Z
Wu
C
C
Zhou
P
P
Dai
D
D
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015764:Bepridil / Q000494:pharmacology*; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology*; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D017966:Pyramidal Cells / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D015222:Sodium Channels; D015764:Bepridil; D011188:Potassium