Studies On The Effects Of Taurine-Magnesium Coordination Compound On The Arrhythmias Induced By Ouabain

Objective: To study the antiarrhythmic activity of taurine-magnesium coordination compound (TMC) in vivo by using the arrhythmic model induced by ouabain of guinea pig. Whole cell patch clamp technique and two microelectrode voltage clamp technique were used to characterize the effects of TMC on the action potential (AP) and L-type calcium channel of guinea pig ventricular myocytes, and the inward rectifier potassium channel (Kir2.1) expressed in xenopus oocytes.Methods: 1. The effects of TMC on cardiotoxicity induced by ouabain in guinea pigs were studied through intravenous administration of 10mg-Kg"^ 20 mg-Kg'W 40mg-Kg~' TMC. The occurrence of arrhythmias including ventricular premature (VP), ventricular tachycardia (VT), ventricular fibrillation (VF) and death, and the accumulating concentrations of ouabain to produce the above arrhythmias were recorded and compared with Smg-Kg"1 lidocaine. 2. Single guinea pig ventricular myocytes were obtained by Langendroff perfusion. Only the cells with rod shaped and clear cross striations were used for experiments. Whole cell patch clamp was applied to record the AP and the L-type calcium current (Ica-t) in isolated ventricular myocytes at room temperature. Measurements were made of the followings: resting membrane potential (RMP), overshot (OS), action potential duration at 50% and 90% of repolarization (APDso and APDgo) and the amplitude of the calcium currents. Currents were normalized relative to cell capacitances. The above parameters were measured again after TMC (100, 200, 400 or 800 u mol-L"1) administration. The current-voltage relationships (I-V curves) and the activation curves were performed. 3. Xenopus oocytes expressing human inward rectifierpotassium channel Kir2.1 obtained by gene technique. Oocytes were voltage clamped in 100 u mol-L-1 or 200 u mol-L-1 TMC solution (perfusion rate 2ml-min-1), and records were done using the appropriate voltage protocols. The stimulus was ranging from -80mV to +80mV, and the pulse duration was 120ms.Results: 1. 20mg.Kg-1 TMC reduced the heart rates of guinea pigs, which was similar to that of 3mg.Kg-1 lidocaine. 20mg-Kg-1, 40mg-Kg-1 TMC or Smg-Kg-1 lidocaine could delay the occurrence of arrhythmias induced by ouabain, and increase the accumulating concentrations of ouabain. 2. TMC at 1 OOP mol-L-1 or 200 u mol-L-1 prolonged APDso and APDgo. 3. The current density of Ica ?L of guinea pig ventricular myocytes increased after exposed to 100 u mol-L-1 or 200 u mol-L-1 TMC, while no significant effect was found on Kir2.1 channel.Conclusion: 1 . Antiarrhythmic activity of TMC was observed in vivo, which might correlate with the prolongation of APD after exposure to 100 u mol.L-1 or 200 y mol-L-1 TMC in vitro. The increase of Ica.L could contribute to the prolongation of APD. 2. TMC at 100u mol.L-1 or 200 u mol-L-1 had no effect on inward rectifier potassium channel, which indicated that TMC didn't affect the RMP and didn't contribute to the prolongation of APD.