Verapamil and TTX inhibit +Vmax but differentially alter the duration of action potential of adult chicken ventricular myocardium.
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1998-04-01
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Verapamil, a Ca2+ channel blocker, is also reported to block Na+ channels in mammalian heart and to modulate the repolarisation phase of cardiac action potential (AP). The Na+ channel blocking activity of verapamil and its implication to changes in repolarisation were studied on chicken ventricular strips where upstroke is due to highly TTX sensitive Na+ channels. At low doses verapamil (0.5-5 micro M) and TTX (0.1-0.5 nM) did not cause any significant effect on resting membrane potential (Em), maximal upstroke velocity (+Vmax) or AP duration (ADP). Higher concentrations of both verapamil (10-320 micro M) and TTX (1-40 nM) caused dose-dependent decrease in +Vmax and overshoot (Eov) without any change in Em. EC50 for the inhibitory effect of verapamil and TTX on +Vmax was 140 microM and 14 nM respectively. Na+ channels in adult chicken ventricular myocardium, therefore, seem to be more sensitive to TTX than their mammalian counterpart. Higher dosage of verapamil are needed to block Na+ channels in adult avian heart as reported for mammalian myocardium. Both verapamil and TTX caused dose-dependent changes in APD at-20 mV (ADP20) and at 90% repolarisation (APD90). TTX (1-40 nM) produced a decrease of 5-13% in APD20 and 4-12% in APD90 indicating a uniform hastening of the repolarisation process. Verapamil (10-320 micro M), however, induced 6-38% decrease in APD20 but 5-12% increase in APD90. Regression analysis of the relationship between changes in +Vmax and APD20 and APD90 in presence of TTX and verapamil exhibit significant linear correlation r for APD20 and APD90, being +0.965 for TTX and +0.978 and-0.898 for verapamil respectively. A linear correlation between inhibition of +Vmax and reduction in APD for TTX indicates the possibility that Na+ channel linked mechanism(s) underlie repolarisation process. Verapamil induced decrease in APD20 and increase in APD90 could be explained by the block of Na+/Ca2+ and K+ channels respectively.
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Prakash P, Tripathi O. Verapamil and TTX inhibit +Vmax but differentially alter the duration of action potential of adult chicken ventricular myocardium. Indian Journal of Biochemistry & Biophysics. 1998 Apr; 35(2): 123-30