Abstract 15165: A Green Tea Catechin, (-)-epicatechin-3-gallate, Suppresses Early After-depolarization in Long-term Cultured Cardiomyocytes
Introduction: Our previous study verified (-)-epicatechin-3-gallate (ECG), a green tea polyphenol, can act as a sodium channel agonist. However, the treating effects of ECG on the arrhythmic disorders, such as early after-depolarization (EAD) remain uncertain.
Hypothesis: We hypothesize that ECG alters the rate of spontaneous action potential (sAP) and suppresses EAD through its action on voltage-gated sodium current (INa).
Methods: By using patch-clamp technique, we characterized the alterations of sAP in cultured neonatal rat ventricular myocytes (NRVMs). We further examined the effects of ECG on the firing rate and morphology of sAP.
Results: The sAP alterations were investigated in two stages. The early stage, 3-4 days post cell isolation, involved a gradual suppression of amplitude (~36.9%) and frequency (~72%) in the early culture periods, followed by about two folds APD90 prolongation in the late culture stage, > 7 days post cell isolation. These changes of sAP were strongly correlated with dysfunction of INa (r2=0.99) but not with IK or Ito. With an increment in the incubating period, the INa properties were also observed in the decrease of INa density (~44%), negative shift of steady-state inactivation curve (Vh, -73.4±4.2 vs. 83.1±4.7 mV, p<.05), and prolongation of the recovery time constant (τ, 65.8±4.1 vs. 82.5±4.6 ms, p<.05). The dysfunction of INa appeared to result in an increased incidence of the bradycardia-dependent EAD. Treatment with ECG suppressed EAD via accelerating the INa recovery time to normal, resulting in fast firing rate of the sAP as in early culture period.
Conclusions: Long-term culture of myocytes leads to retardation of automaticity, APD prolongation, EAD occurrence, and concomitant INa suppression. ECG restores INa and cellular automaticity in long-term cultured NRVMs.
Author Disclosures: A.Z. Wu: None. S. Wu: None. C. Lin: None. S. Lin: None.
- © 2014 by American Heart Association, Inc.