Small Conductance Calcium Activated Potassium Channels and Cardiac Arrhythmia
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概要
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The mechanisms of arrhythmia in heart failure (HF) is attributed in part to the reduced repolarization reserve resulted from an upregulation of late Na<SUP>+</SUP> current and the downregulation of multiple major K currents (<I>I</I><SUB>to</SUB>, <I>I</I><SUB>KS</SUB>, <I>I</I><SUB>Kr</SUB> and <I>I</I><SUB>K1</SUB>). In addition, <I>I</I><SUB>KATP</SUB> is defective in HF, further reducing the ability of failing cells to shorten action potential duration (APD) during metabolic stress. While studying rabbit hearts with HF, Dr. Masahiro Ogawa made an unexpected observation that there is acute but reversible APD shortening after fibrillation-defibrillation episodes in failing (but not normal) rabbit ventricles. In addition, there are multiple spontaneous ventricular fibrillation (SVF) episodes after defibrillation shocks in rabbit hearts with most severe APD shortening. Recurrent SVF in HF might be due to increased diastolic Ca<SUP>2+</SUP>-membrane potential coupling gain due to downregulation of <I>I</I><SUB>K1</SUB>, as reported by Dr. Mitsunori Maruyama. However, the acute APD shortening may also play a role in SVF by promoting late phase 3 early afterdepolarization (EAD) and triggered activity, leading to SVF. Chua et al. subsequently documented that upregulation of the apamin-sensitive potassium current (<I>I</I><SUB>KAS</SUB>), a current conducted through the small conductance Ca<SUP>2+</SUP> activated K<SUP>+</SUP> channels, is responsible for postshock APD shortening. These findings suggest that <I>I</I><SUB>KAS</SUB> upregulation increases repolarization reserve of HF but may also be proarrhythmic by excessive shortening of APD. <I>I</I><SUB>KAS</SUB> may be a novel target for antiarrhythmic therapy for ventricular arrhythmias.