IONIC MECHANISM RESPONSIBLE FOR PROLONGATION OF CARDIAC ACTION-POTENTIAL DURATION BY BERBERINE

This study was designed to investigate the effects of berberine on mem brane currents Forming the repolarization phase of action potentials i n isolated guinea pig ventricular myocytes by using the patch-clamp te chnique. Application of berberine (3-30 mu M) to the current-clamped m yocytes produced a significant prolongation of action-potential durati on (APD), which was concentration dependent. However, this agent (3-30 mu M) did not affect the resting potential and action-potential ampli tude. The prolongation of APD caused by berberine was not attenuated b y tetrodotoxin (TTX, 10 mu M), and TTX (10 mu M) failed to shorten APD in cells pretreated with 30 mu M berberine. Under the voltage-clamp c onditions, berberine (3-30 mu M) inhibited the delayed rectifier K+ cu rrents (I-K) Under conditions in which the rapidly activating componen ts (I-Kr) and slowly activating component (I-Ks) were dissected out, b erberine was shown to block I-Ks without affecting I-Kr. Application o f berberine (3-30 mu M) increased the Na+-Ca2+ exchange currents, whic h were completely abolished by 5 mM NiCl. The L-type Ca2+ currents (I- Ca) also were increased by 3-30 I-IM berberine, but the threshold pote ntial, the potential at which Ic, was maximal, and the apparent revers al potential remained unchanged. Berberine at either 3 or 30 mu M did not affect the inward rectifier K+ currents. This study suggests that the prolongation of cardiac repolarization by berberine is mainly caus ed by the inhibition of I-Ks and increase of I-Ca.