| Background:Peak-fomix-like action potential configuration, which is induced by outward flow of ionic current on the end of I phase repolarization in action potential, is one of the extrem protruded electrophysiological characteristics of right ventricular epicardial cells (Epi), and also the important ions basis of"all or none"phase II repolarization, uneven loss of berm in action potential and 2 phase reentry. Ventricular tachycardia and ventricular fibrillation (VT/VF) induced by cutty cycle of ectopic premature contract on the basis of 2 phase reentry, might be the main pathophysiological mechanism of sudden death in Brugada syndrome as the same as that in right ventricular malignant arrhythmia. Several ion currents participate in the equilibrium of 1 phase repolarization, such as transient outward potassium current (Itol), calcium-dependent chlorinecurrent (Ito2), L-type calcium current, calcium-natrium exchange current and delayed natrium current. In addition, the current strength of Itol is much greater than the others in 1 phase repolarization, and L type calcium current is the most important inward ionic current in plateau phase repolarization, which plays a significant role in the plateau phase action potential. Thus, it might be an important strategy to inhibit outward shift of ionic current in 1 phase repolarization of right ventricle, especially Itol current for Brugada syndrome theropy. Inforced L-type calcium current might benefit the recovery of plateau phase of action potential so as to reduce or eliminate the uneven phenomenon in plateau phase of action potential. The study outcome of cellular electrophysiological mechanism about Brugada syndrome provides theoretic possibility for its prevention and therapy. Any drugs or measures could nomalize phenotype of Brugada syndrome, reduce ventricular arrhythmia events and electric storm if they could inhibit outward current including transient outward potassium current, ATP sensitive potassium current and delayed rectification potassium current on the end of 1 phase action potential, or increase inward current including L type calcium current and sodium current. Miyazaki et al reported thatβ-receptor stimulants decrease ST segment elevation extent in right precordial leads, even to normal in patients with Brugada syndrome. In some studies Isoproterenol has been demonstrated to reduce ventricular arrhythmia events and electric storm occurrence. But the exact physiological mechanism remains unknown. Aim: in the present study patch clamp technique was adopted to investigate the effect of Isoproterenol on action potential duration, transient outward potassium current and L type calcium current in rabbit right ventricular epicardium cells.Objective:This study aimed to explore the possible physiological mechanism of Isoproterenol preventing Brugada syndrome from ventricular arrhthmia events and to provide theoretic evidences for treatment of related diseases.Methods:Single epicardial myocytes of right ventricle of the rabbits were isolated with enzymatic dissociation and separation. The whole-cell patch clamp recording technique was used to observe the effect of 1μM isoproterenol on action potential duration(APD),transient outward potassium current(Ito) and L-calcium current (ICa , L) in epicardial myocytes of right ventricle of the rabbits. Results:(1) 1μM Iso obviously prolonged APD20,APD50 and APD90 from (168±20)ms,(257±24)ms, and (416±33)ms to (316±31)ms,(265±23)ms and ()ms (27.0%,52.2%; 24.0%,35.6%, n=16, p<0.05) , respectively.(2) At +60mv, 1μM Iso reduced Ito from 11.4+1.7 pA/pF to 6.3+0.5 pA/Pf (n=16, p<0.05), descended Ito I-V curve without activation potential, peak potential and reversing potential. Further more, it also induced shift left of Ito homeostasis inactivation curve and shift right of devitalized recovery curvery curve, but no notable effect on half activation voltage of activation curve and activation constant.(3) 1μM Iso increased peak of ICa,L from -6.1+0.6 pA/pF to -8.6+0.9pA/pF (n=10. p<0.05), decreased ICa,L I-V but no change of activation potential, peak potential and reversed potential.Conclusions:(1) Iso could prolong action potential duration, especially APD20 and APD50.(2) Iso could inhibit Ito voltage-dependently in its inactive state.(3) Iso could increase Ica voltage-dependently but didn't change activation potential, peak potential and reversed potential. The above effects of Iso might be the important mechanism for its reduction of ST segment elevation in right precordial leads, ventricular arrhythmia and electric storm in Brugada syndrome.
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