Effects of Propafenone on Action Potential of Rabbit Ventricular Myocytes and the Use-dependent Block of Transient Sodium Current / 中国循环杂志

ABSTRACT

Objective: To study the effects of propafenone on action potential (AP) of rabbit ventricular myocytes with the tonic block and use-dependent block of transient sodium current (INa-T). Methods: A total of 10 adult New Zealand white rabbits were sacriifced and 10 individual ventricular myocytes were isolated by enzyme digestion method. Microelectrode technologies were used to record AP-related parameters maximum diastolic potential (MDP), maximum rate of rise of the action potential upstroke (Vmax), action potential amplitude (APA) and action potential duration at 20%, 50% and 90% (APD20, APD50 and APD90).INa-T was measured, I-V curves and peak currents at different frequencies were detected by whole cell patch clamp before and after propafenone perfusion at 10 μmol/L. Results: There was no statistical difference in MDP at before and after propafenone perfusion as (-80 ± 6) mV vs (-82 ± 5) mV,P>0.05. After perfusion, APA was signiifcantly decreased as (95 ± 12) mV vs ( 125 ± 10) mV,P0.05, (16 ± 3) ms vs (12 ± 3) ms,P>0.05 and (86 ± 14) ms vs (85 ± 12) ms,P>0.05. After propafenone perfusion, I-V curve ofINa-T was shifted upward and the peak current was decreased as (3001 ± 383) pA vs (4193 ± 378) pA, P0.05. After perfusion, no significant use-dependent block was observed when stimulated at 0.06 Hz and 1 Hz,P>0.05, while at 2 Hz, 5 Hz and 10 Hz, propafenone perfusion demonstrated signiifcant use-dependent block uponINa-T with the inhibition fractions of (22 ± 11)%, (38 ± 14)% and (52 ± 17)% respectively, those were signiifcantly different from the inhibition fractions at either 0.06 Hz or 1Hz,P<0.05. When the inhibition fractions were compared by each 2 conditions, allP<0.05. Conclusion: Propafenone may slow down the Vmax of AP, reduce APA and without the impact on APD; the effects onINa-T is not only in tonic block, but also more obviously in use-dependent block in isolated ventricular myocytes of New Zealand rabbit. Such inlfuences minimized the impact on QT interval and meanwhile, decreased the incidence of brad arrhythmia.