The ion targets of arrhythmias induced by ouabain and aconitine in guinea pig and rat ventricular myocytes / 药学学报

<p><b>AIM</b>To observe the effects of ouabain and aconitine on APD and ion channels in isolated guinea pig and rat ventricular myocytes; to elucidate the action mechanisms of these two drugs and set up new arrhythmic models on cellular level.</p><p><b>METHODS</b>In isolated ventricular myocytes of guinea pig and rat, the effects of ouabain and aconitine on APD, ICa-L, Ik, Ito and Ik1 were observed using the whole cell patch clamp technique.</p><p><b>RESULTS</b>Ouabain (5 micromol x L(-1)) obviously prolonged the APD90, increased ICa-L, decreased Ik and Ik1 in guinea pig ventricular myocytes. Aconitine (1 micromol x L(-1)) lengthened the APD90, increased ICa-L, decreased Ito and increased Ik1 in rat ventricular myocytes.</p><p><b>CONCLUSION</b>The targets on ouabain- and aconitine-induced arrhythmias included APD, ICa-L, Ik, Ito, and Ik1. APD, ICaL, Ik and Ito must be the powerful ones, both in arrhythmic and antiarrhythmic courses. The ouabain- and aconitine- induced arrhythmic models on cellular level were built to study the antiarrhythmic mechanisms of chemicals and evaluate new drugs. These two new-type models in vitro were stable, liable, repeatable and economic, which were superior to those typical models in vivo.</p>

Comparison of the anti-arrhythmic effects of matrine and berbamine with amiodarone and RP58866 / 药学学报

<p><b>AIM</b>To clarify mechanisms that the antiarrhythmic effects of matrine and berbamine are weaker than those of amiodarone and RP58866.</p><p><b>METHODS</b>Experimental arrhythmic models were induced by aconitine, coronary artery ligation and electric stimulation in rats and rabbits. Whole-cell patch-clamp techniques were used to record IK1, IKr, IKs and Ito.</p><p><b>RESULTS</b>Matrine and berbamine significantly increased the dose of aconitine for induction of ventricular premature and ventricular tachycardia in rats, decreased the number of arrhythmias induced by coronary artery ligation in rats and increased ventricular fibrillation threshold (VFT) induced by electric stimulation in rabbits, but the anti-arrhythmic potency of matrine and berbamine was lower than that of amiodarone and RP58866. The inhibitory actions of matrine and berbamine on IK1, IKr, IKs, Ito were lower than those of amiodarone and RP58866. The IC50 of matrine for IK1, IKr, IKs, Ito were (46 +/- 3), (32.9 +/- 1.2), (37 +/- 8) and (7.6 +/- 0.5) mol x L(-1), respectively. The IC50 of amiodarone for IK1, IKr, IKs, Ito were (21 +/- 5) , (3.7 +/- 0.7), (5.9 +/- 0.9) and (5.9 +/- 0.6) mol x L(-1), respectively.</p><p><b>CONCLUSION</b>The inhibitory actions of matrine and berbamine on IK1, IKr, IKs, Ito were lower than those of amiodarone and RP58866, which might be the reason that the antiarrhythmic effects of matrine and berbamine were weaker than those of amiodarone and RP58866.</p>