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Our recent data show that in cardiac myocytes polyunsaturated fatty acids (PUFAs) are antiarrhythmic. They reduce I Na , shorten the action potential, shift the threshold for excitation to more positive potentials, and prolong the relative refractory period. In this study we use patch-clamp techniques in whole-cell mode and confocal Ca 2؉ imaging to examine the effects of PUFAs on the voltage-gated L-type Ca 2؉ current (I Ca,L ), elementary sarcoplasmic reticulum Ca 2؉ -release events (Ca 2؉ -sparks), and [Ca 2؉ ] i transients in isolated rat ventricular myocytes. Extracellular application of eicosapentaenoic acid (EPA; C20:5 n ؊ 3) produced a prompt and reversible concentration-dependent suppression of I Ca,L . The concentration of EPA to produce 50% inhibition of I Ca was 0.8 M in neonatal rat heart cells and 2.1 M in adult ventricular myocytes. While the EPA induced suppression of I Ca,L , it did not significantly alter the shape of the current-voltage relation but did produce a small, but significant, negative shift of the steady-state inactivation curve. The inhibition of I Ca,L was voltage-and time-dependent, but not use-or frequency-dependent. Other PUFAs, such as docosahexaenoic acid, arachidonic acid, linolenic acid, linoleic acid, conjugated linoleic acid, and eicosatetraynoic acid had similar effects on I Ca,L as EPA. All-trans-retinoic acid, which had been shown to suppress induced arrhythmogenic activity in rat heart cells, also produced a significant inhibition of I Ca,L . The saturated stearic acid and the monounsaturated oleic acid had no effect on I Ca,L . Because both I Ca,L and sarcoplasmic reticulum Ca 2؉ -release underlie many cardiac arrhythmias, we examined the effects of EPA on I Ca,L and Ca 2؉ -sparks. While EPA suppressed both, it did not change the temporal or spatial character of the Ca 2؉ -sparks, nor did it alter the ability of I Ca,L to trigger Ca 2؉ -sparks. We conclude that PUFAs may act as antiarrhythmic agents in vivo in normal and Ca 2؉ -overloaded cells principally because they reduce Ca 2؉ entry by blocking I Ca,L . Furthermore, PUFAs act directly to decrease I Na and I Ca,L , but indirectly to reduce the [Ca 2؉ ] i transients and [Ca 2؉ ] i -activated membrane current. Although a negative inotropic action is associated with application of PUFAs, it is clear that by reducing I Ca,L , I Na and Ca 2؉ -sparks, PUFAs can reduce spontaneous extrasystoles in the heart. The mechanisms by which PUFAs act are discussed.

Massive loss of cardiac myocytes after myocardial infarction (MI) is a common cause of heart failure. The present study was designed to investigate the improvement of cardiac function in MI rats after embryonic stem (ES) cell transplantation. MI in rats was induced by ligation of the left anterior descending coronary artery. Cultured ES cells used for cell transplantation were transfected with the marker green fluorescent protein (GFP). Animals in the treated group received intramyocardial injection of ES cells in injured myocardium. Compared with the MI control group injected with an equivalent volume of the cell-free medium, cardiac function in ES cell-implanted MI animals was significantly improved 6 wk after cell transplantation. The characteristic phenotype of engrafted ES cells was identified in implanted myocardium by strong positive staining to sarcomeric alpha-actin, cardiac alpha-myosin heavy chain, and troponin I. GFP-positive cells in myocardium sectioned from MI hearts confirmed the survival and differentiation of engrafted cells. In addition, single cells isolated from cell-transplanted MI hearts showed rod-shaped GFP-positive myocytes with typical striations. The present data demonstrate that ES cell transplantation is a feasible and novel approach to improve ventricular function in infarcted failing hearts.