Effects of Propafenone on Action Potential of Rabbit Ventricular Myocytes and the Use-dependent Block of Transient Sodium Current
10.3969/j.issn.1000-3614.2015.07.016
- VernacularTitle:普罗帕酮对兔心室肌细胞动作电位的影响及对快钠电流的使用依赖性阻滞作用
- Author:
Jing LI
;
Xiaoyun ZHENG
;
Gang ZHOU
;
Yuetao ZHAO
;
Zhen YANG
- Publication Type:Journal Article
- Keywords:
Propafenone;
Action potential;
Transient sodium current;
Tonic block;
Use-dependent block
- From:
Chinese Circulation Journal
2015;(7):679-683
- CountryChina
- Language:Chinese
-
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,P<0.05, the Vmax slowed down as (330 ± 43) V/s vs (420 ± 54) V/s,P<0.05, while APD20, APD50 and APD90 were unchanged as (8 ± 2) ms vs (6 ± 2) ms,P>0.05, (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, P<0.05. Before perfusion, when stimulated at 0.06 Hz, 1 Hz, 2 Hz, 5 Hz and 10 Hz, there were no signiifcant use-dependent block inINa-T , and no real difference inINa-T between the 10th and 1st pulse,P>0.05. 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.
