Azimilide at 1 microM prolonged action potential duration by 25% and 17% at 0.33 and 1 Hz in canine ventricular myocytes, but had variable effects at 5 microM due to multiple current blockades.
Does azimilide affect action potential duration and membrane currents in canine ventricular myocytes?
Azimilide exerts concentration-dependent effects on action potential duration in canine ventricular myocytes, acting as a Class III antiarrhythmic primarily at low concentrations (< 5 microM).
INTRODUCTION: Azimilide (NE-10064) has antiarrhythmic and antifibrillatory effects in canine models of ventricular arrhythmia. The goal of the present study was to examine the effects of azimilide on action potential and membrane currents of canine ventricular myocytes. METHODS AND RESULTS: Membrane voltage and current were recorded using the whole cell, patch clamp method. Azimilide at 1 microM induced a consistent prolongation of action potential duration (APD): on average APD90 was prolonged by 25% and 17% at stimulation rates of 0.33 and 1 Hz, respectively. Elevating the drug concentration to 5 microM induced APD prolongation in some cells but APD shortening in the others at 0.33 Hz, and a consistent APD shortening at 1 Hz. Azimilide suppressed the following currents (Kd in parenthesis): IKr ( or = 50 microM at +50 and -140 mV, respectively). Azimilide blocked IKr, IKs, and INa in a use-dependent manner. Furthermore, azimilide reduced a slowly inactivating component of Na current that might be important for maintaining the action potential plateau in canine ventricular myocytes. CONCLUSION: Azimilide has variable effects on APD in canine ventricular myocytes due to its blocking effects on multiple currents with different potencies. Its Class III antiarrhythmic action is most likely seen at low concentrations (< 5 microM).
Yao et al. (Sat,) conducted a other in Ventricular arrhythmia. Azimilide (NE-10064) was evaluated on Action potential duration (APD) and membrane currents. Azimilide at 1 microM prolonged action potential duration by 25% and 17% at 0.33 and 1 Hz in canine ventricular myocytes, but had variable effects at 5 microM due to multiple current blockades.
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