3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) and
p-methoxycinnamic acid (PMCA) have been identified as the major bioactive components in the serum collected from rats treated with oral administration of Polygalae Radix (“YuanZhi,” the roots of
Polygala tenuifolia W
ILLD.), a traditional Chinese medicine used to relieve insomnia, anxiety and heart palpitation. The present study was designed to investigate its direct electrophysiological effects on isolated ventricular myocytes from rabbits. Whole-cell configuration of the patch-clamp technique was used to measure action potential (AP) and membrane currents in single ventricular myocytes enzymatically isolated from adult rabbit hearts. Ca
2+ transients were recorded in myocytes loaded with the Ca
2+ indicator Fluo-4AM. Among three bioactive substances of Polygala metabolites, only M-TMCA (15–30 µ
M) significantly shortened action potential duration at 50% and 90% repolarization (APD
50 and APD
90) in cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also inhibited L-type calcium current (
ICa,L), but showed effect on neither transient outward potassium current (
Ito) nor steady-state potassium current (
IK,SS). Furthermore, M-TMCA abolished isoprenaline plus BayK8644-induced early afterdepolarizations (EADs) and suppressed delayed afterdepolarizations (DADs) and triggered activities (TAs). This potential anti-arrhythmic effects were likely attributed by the inhibition of
ICa,L and the suppression of intracellular Ca
2+ transients, which consequently suppress the generation of transient inward current (
Iti). These findings suggest that M-TMCA may protect the heart from arrhythmias
via its inhibitory effect on calcium channel.
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