Effects of anandamide on potassium channels in rat ventricular myocytes: a suppression of I(to) and augmentation of K(ATP) channels.

Anandamide is an endocannabinoid that has antiarrhythmic effects through inhibition of L-type Ca(2+) channels in cardiomyocytes. In this study, we investigated the electrophysiological effects of anandamide on K(+) channels in rat ventricular myocytes. Whole cell patch-clamp technique was used to record K(+) currents, including transient outward potassium current (I(to)), steady-state outward potassium current (I(ss)), inward rectifier potassium current (I(K1)), and ATP-sensitive potassium current (I(KATP)) in isolated rat cardiac ventricular myocytes. Anandamide decreased I(to) while increasing I(KATP) in a concentration-dependent manner but had no effect on I(ss) and I(K1) in isolated ventricular myocytes. Furthermore, anandamide shifted steady-state inactivation curve of I(to) to the left and shifted the recovery curve of I(to) to the right. However, neither cannabinoid 1 (CB(1)) receptor antagonist AM251 nor CB(2) receptor antagonist AM630 eliminated the inhibitory effect of anandamide on I(to). In addition, blockade of CB(2) receptors, but not CB(1) receptors, eliminated the augmentation effect of anandamide on I(KATP). These data suggest that anandamide suppresses I(to) through a non-CB(1) and non-CB(2) receptor-mediated pathway while augmenting I(KATP) through CB(2) receptors in ventricular myocytes.

Effect of polydatin on action potential in ventricular papillary muscle of rat and the underlying ionic mechanism.

It is proved that polydatin has cardioprotection against ischemia-induced arrhythmia, but the electrophysiological mechanism is not clear. The aim of the present study was to investigate the effect of polydatin on action potential (AP) in ventricular papillary muscle and the underlying ionic mechanism in rat using intracellular recording and whole-cell patch clamp techniques. The results showed: (1) In normal papillary muscles, polydatin (50 and 100 µmol/L) shortened duration of 50% repolarization (APD(50)) and duration of 90% repolarization (APD(90)) in a concentration-dependent manner (P<0.01). But polydatin had no effects on resting potential (RP), overshoot (OS), amplitude of action potential (APA) and maximal rate of depolarization in phase 0 (V(max)) in normal papillary muscles (P>0.05). (2) In partially depolarized papillary muscles, polydatin (50 µmol/L) not only shortened APD(50) and APD(90) (P<0.05), but also decreased OS, APA and V(max) (P<0.05). (3) After pretreatment with glibenclamide (10 µmol/L), an ATP-sensitive K(+) channel blocker, the electrophysiological effect of polydatin (50 µmol/L) was partially inhibited. (4) Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a nitric oxide (NO) synthase inhibitor, failed to abolish the effect of polydatin (50 µmol/L) on AP. (5) Polydatin (25, 50, 75 and 100 µmol/L) decreased L-type Ca(2+) current in ventricular myocytes in a concentration-dependent manner (P<0.05). (6) Polydatin (50 µmol/L) increased ATP-sensitive K(+) current in ventricular myocytes (P<0.05). The results suggest that polydatin can shorten the repolarization of AP in normal papillary muscle and inhibit AP in partially depolarized papillary muscle, which might be related to the blocking of L-type Ca(2+) channel and the opening of ATP-sensitive K(+) channel.