Increase in action potential duration and inhibition of the delayed rectifier outward current I_K by berberine in cat ventricular myocytes

Abstract

1In the present work, the effects of the antiarrhythmic drug, berberine, on action potential and ionic currents of cat ventricular myocytes were studied. 2 Berberine prolonged action potential duration in cat ventricular myocytes without altering other variables of the action potential. 3 The drug at concentrations of 0.3-30 gM blocked only the delayed rectifier (IK) current with an IC50 = 4.1 gM. Berberine produced a tonic block and a phasic block that was increased with the duration of the depolarizing pulse. The blocking effect on IK was use-dependent, but not frequency-dependent. 4 In cardiac preparations two delayed rectifier currents have been found: a rapid ('Kr) current and a slow (IKs) current. In the present work it has been found that berberine at the concentrations used, selectively blocked IKr 5 At concentrations higher than 10 gM it also decreased the transient outward (Itol) current. The drug did not have effects on the inward rectifier (IKI) or the high threshold calcium current ('CaL).6 These results show that berberine is a specific potassium channel blocker. The increase in action potential duration induced by berberine can be explained mainly by its blocking effects on IK-

Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential — A safety approach

“…Berberine was earlier described to inhibit hERG potassium current in HEK cells expressing hERG channels [8], to block I Kr current in cardiac myocytes [6], and to increase action potential duration on cardiac preparations [6,7], which are well in line with our findings. Furthermore from this subgroup, we have also studied coptisine, the main alkaloid of C. majus.…”

“…Among these alkaloids, berberine was reported to inhibit hERG potassium current in transfected HEK cells expressing hERG channels [7][8][9], to block delayed rectifier potassium (I Kr ) current in cardiac myocytes [6], and to increase action potential duration on cardiac preparations [6,7]. Chelerythrine was also described to inhibit hERG current [10] and prolong action potential [12].…”

“…However, several studies have demonstrated that berberine [6][7][8][9], chelerythrine [10], chelidonine [11], sanguinarine [11], and protopine [11] have hERG ion channel activities. The human ether-à-go-go-related gene (hERG, KCNH2, Kv11.1) encodes a cardiac voltage-gated potassium channel that provides the major repolarizing current (rapidly activating delayed rectifier potassium current, I Kr ) in phase 3 of the cardiac action potential.…”

Cardiovascular Actions of Berberine

“…In contrast, berberine has no effect on inwardly rectifier K + channels (46). The similar K + channel blocking action was also observed for berberine within the same concentration range (IC 50 = 4.1 ìM) in cat ventricular myocytes (40). There are, however, conflicting reports in the literature on the effect of berberine on cardiac voltagegated Ca 2+ currents.…”

Profile of IKs During the Action Potential Questions the Therapeutic Value of IKs Blockade

“…The current was detected also in other tissues, like vascular smooth muscle [16], embryonic xenopus muscle [17], vestibular dark cells [18], and pancreatic acinar cells [19]. Within a short period of time the current was identified in numerous vertebrate species, including shark [20], bullfrog [21,22], calf [23], rabbit [24], cat [25], guinea pig [26], dog [27] and men [28]. Sanguinetti and Jurkiewicz [29] demonstrated that the delayed rectifier current is composed of two distinct components namely; the rapid (I Kr ) and slow (I Ks ) components of I K .…”