VERAPAMIL AND TTX INHIBIT -MAX BUT DIFFERENTIALLY ALTER THE DURATION OF ACTION-POTENTIAL OF ADULT CHICKEN VENTRICULAR MYOCARDIUM(V)

Verapamil, a Ca2+ channel blocker, is also reported to block Na+ chann els in mammalian heart and to modulate the repolarisation phase of car diac action potential (AP). The Na+ channel blocking activity of verap amil and its implications to changes in repolarisation were studied on chicken ventricular strips where upstroke is due to highly TTX sensit ive Na+ channels. At low doses verapamil (0.1-5 mu M) and TTX (0.1-0.5 nM) did not cause any significant effect on resting membrane potentia l (Em), maximal up-stroke velocity (+V-max) or AP duration (APD). High er concentrations of both verapamil (10-320 mu M) and TTX (1-40 nM) ca used dose-dependent decrease in +V-max and overshoot (Eov) without any change in Em. EC50 for the inhibitory effect of verapamil and TTX on +V-max was 140 mu M and 14 nM respectively. Na+ channels in adult chic ken ventricular myocardium, therefore, seem to be more sensitive to TT X than their mammalian counterpart. Higher doses of verapamil are need ed to block Na+ channels in adult avian heart as reported for mammalia n myocardium. Both verapamil and TTX caused dose-dependent changes in APD at -20 mV (APD(20)) and at 90% repolarisation (APD(90)). TTX (1-40 nM) produced a decrease of 5-13% in APD(20) and 4-12% in APD(90) indi cating a uniform hastening of the repolarisation process. Verapamil (1 0-320 mu M), however, induced 6-38% decrease in APD(20) but 5-12% incr ease in APD(90). Regression analysis of the relationship between chang es in +V-max and APD(20) and APD(90) in presence of TTX and verapamil exhibit significant linear correlation r for APD(20) and APD(90), bein g +0.981 and +0.965 for TTX and +0.978 and -0.898 for verapamil respec tively. A linear correlation between inhibition of +V-max and reductio n in APD by TTX indicates the possibility that Na+ channel linked mech anism(s) underlie repolarisation process. Verapamil induced decrease i n APD(20) and increase in APD(90) could be explained by the block of N a+/Ca2+ and K+ channels respectively.