|Title:||Sensitivity of the Slow Component of the Delayed Rectifier Potassium Curren (Iks)Topotassium Channel Blockers: Implications for Clinical Reverse Use-Dependent Effect||Authors:||LAI, LING-PING||Keywords:||antiarrhythmic agents;potassium channels;voltage clamp;III ANTIARRHYTHMIC AGENTS;HUMAN VENTRICULAR MYOCYTES;HUMAN ATRIAL MYOCYTES||Issue Date:||1999||Journal Volume:||v.6||Journal Issue:||n.4||Start page/Pages:||251-259||Source:||JOURNAL OF BIOMEDICAL SCIENCE||Abstract:||
The slow delayed rectifier potassium current (I-Ks) is unique in its slow activation and deactivation kinetics. It is important during cardiac repolarization, especially when the heart rate is fast. We compared the effects of quinidine , procainamide, sotalol, and amiodarone on I-Ks and correlated the findings with the clinical reverse use- dependent effects of potassium channel blockers. Human minK RNA was obtained by reverse transcription-polymerase chain reaction using explanted human heart. The RNA was injected into Xenopus oocytes for heterologous expression of I-Ks. A two-electrode voltage clamp technique was performed to investigate the I-Ks. We demonstrated that quinidine, sotalol and procainamide had no effects on I-Ks up to a concentration of 300 mu M while amiodarone inhibited I-Ks in a concentration-dependent manner starting from 10 mu M. The inhibition by amiodarone was state-dependent with gradual unblocking after depolarization, The degree of inhibition was 53% immediately after depolarization and 19% at the end of a 5-second depolarization. I-Ks is 30 times more sensitive to amiodarone than to quinidine, sotalol, and procainamide, Quinidine, sotalol and procainamide have reverse use- dependent effects while amiodarone does not, This is compatible with the hypothesis that no inhibition of I-Ks at clinical concentrations contributes to the clinical reverse use-dependent effects.
|Appears in Collections:||醫學系|
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