Ionic mechanism responsible for prolongation of cardiac action-potential duration by berberine.
This study was designed to investigate the effects of berberine on membrane currents forming the repolarization phase of action potentials in isolated guinea pig ventricular myocytes by using the patch-clamp technique. Application of berberine (3-30 microM) to the current-clamped myocytes produced a significant prolongation of action-potential duration (APD), which was concentration dependent. However, this agent (3-30 microM) did not affect the resting potential and action-potential amplitude. The prolongation of APD caused by berberine was not attenuated by tetrodotoxin (TTX, 10 microM), and TTX (10 microM) failed to shorten APD in cells pretreated with 30 microM berberine. Under the voltage-clamp conditions, berberine (3-30 microM) inhibited the delayed rectifier K+ currents (I(K)). Under conditions in which the rapidly activating components (I(Kr)) and slowly activating component (I(Ks)) were dissected out, berberine was shown to block I(Ks) without affecting I(Kr). Application of berberine (3-30 microM) increased the Na+-Ca2+ exchange currents, which were completely abolished by 5 mM NiCl. The L-type Ca2+ currents (I(Ca)) also were increased by 3-30 microM berberine, but the threshold potential, the potential at which I(Ca) was maximal, and the apparent reversal potential remained unchanged. Berberine at either 3 or 30 microM did not affect the inward rectifier K+ currents. This study suggests that the prolongation of cardiac repolarization by berberine is mainly caused by the inhibition of I(Ks) and increase of I(Ca).
Wang
Y X
YX
Department of Pharmacology, Fourth Military Medical University, Xian, People's Republic of China.
Zheng
Y M
YM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D001599:Berberine; D013779:Tetrodotoxin; D012964:Sodium