ABSTRACT-To examine taurine actions on the rate of repolarization of action potentials (AP), L-type Ca2+ (Ica), late outward K+ (IK) and the inward rectifier currents as affected by the external Ca2+ concen trations ([Ca2+]o), whole-cell voltage-clamp and current-clamp experiments were conducted in guinea pig ventricular myocytes. At a high (3.6 mM) [Ca 2+]o, 10 mM taurine suppressed both Ica and IK, shortened AP duration and decelerated the rate (-dV/dt) of terminal repolarization of AP. In contrast, at a low (0.9 mM) [Ca2+]o, taurine intensified both Ica and IK, lengthened AP duration and accelerated -dV/dt. However, at either [Ca2+]o, the resting membrane potential was slightly hyperpolarized, and the inward rectifier current examined by the ramp-pulse protocol remained unaffected by taurine. Taurine is suggested to maintain a stable AP duration by altering the inward Ca2+ and IK in the opposite directions, depending on [Ca2+]o. The relevance of the stabilizing action of taurine on the AP duration to its reported anti arrhythmic efficacies is discussed.
Keywords:Taurine, Action potential, Ca2+ channel, K+ channel, Antiarrhythmic actionTaurine, 2-aminoethanesulfonic acid (H2NCH2CH2SO3H), is the most abundant amino acid of the amino acid pool of the heart (50%). Although its plasma level is as low as 0.05 to 0.22 mM, the myocardial level is hundreds of times higher than the plasma level: 5.6 (humans) 28 (rats) mM/kg wet weight (1).During the last decade, much evidence for the cardiac effects of taurine was found (2). Sawamura et al. In 1963, Read and Welty (6) first described that taurine, intracellularly given, could prevent the development of epinephrine-induced premature contractions and ceased the arrhythmias of acute or chronic digitalis toxicity. Later, Chazov et al. (7) (1974) in guinea pig and dog hearts treated with toxic doses of strophathidin-K, Fran coni et al. (8) (1985) in Langendorff-perfused guinea pig hearts exposed to the hypoxia-reoxygenation sequence, and Takahashi et al. (9) (1988) in cultured embryonic mouse heart cells exposed to high and low [Ca 2+]o also confirmed the antiarrhythmic activities of taurine in con centrations of 1-20 mM.The action potential (AP) duration is a major deter minant for the electrical refractory period of the cardiac muscle, and the AP duration is ionically controlled by mainly the inward Ca2+ and the delayed rectifier currents. Also, the inward rectifier current plays a key role in maintaining a stable resting potential (10). The present study was designed to test how taurine altered AP parameters, whether the taurine-induced alterations in AP parameters could provide an antiarrhythmic effect and how the AP alterations are related to the changes in the underlying ionic currents. For this purpose, we ex amined taurine-induced changes in ionic currents in the same ionic environment as in AP recordings for a low and high [Ca 2+]o without using any channel-specific blockers.