Satoh H
Department of Pharmacology, Nara Medical University, Japan.
Adv Exp Med Biol. 1998;442:121-8. doi: 10.1007/978-1-4899-0117-0_16.
During ischemia, hypoxia and cardiac failure, the heart undergoes several adverse changes, including a reduction in taurine (2-aminoethanesulfonic acid). Oral administration of taurine under these disease conditions would be expected to act like a mild cardiac glycoside. Taurine would exert improvement in the accumulation of [Na]i and the loss of alpha-amino acids. Nonetheless, when intracellular taurine content is raised, there would be the benefit of increased Ca2+ release from the sarcoplasmic reticulum and increased Ca2+ sensitivity of the contractile proteins, as well as possible changes in the action potential associated with the actions of taurine on ion channels. In fact, intracellular application of taurine produces the opposite actions to extracellularly administration of the amino acid. From our previous experiments, the electrophysiological actions of taurine on cardiac muscle cells include the following. (a) Prolongation of action potential duration (APD) at high [Ca]i and shortening of APD at low [Ca]i. In multicellular preparations, however, taurine did not always prevent [Ca]o-induced effects. (b) Stimulation of spontaneous activity at low intracellular and extracellular Ca2+ concentrations ([Ca]i and [Ca]o), and vice versa. (c) Inhibition of the L-type Ca2+ current (ICa(L)) at high [Ca]i, and vice versa. (d) Enhancement of the T-type Ca2+ current (ICa(T)). (e) Inhibition of fast Na+ current (INa). (f) Enhancement of TTX-insensitive slow Na+ current. (g) Inhibition of delayed rectifier K+ current (IKrec) at high [Ca]i, and vice versa. (h) Enhancement of the transient outward current (Ito). (i) Inhibition of the ATP-sensitive K+ current (IK(ATP)). Since taurine acts on so many ion channels and transporters, it is clearly non-specific. Although it is very difficult to understand the diversity of taurine's actions, it is possible that taurine can exert its potent cardioprotective actions under the conditions of low [Ca]i, as well as Ca2+ overload. Thus, although taurine-induced modulation of ion channels located on the cardiac cell membrane is complex, the multiple effects may combine to yield useful therapeutic results.
在缺血、缺氧和心力衰竭期间，心脏会发生多种不良变化，包括牛磺酸（2-氨基乙磺酸）含量降低。在这些疾病状态下口服牛磺酸有望起到轻度强心苷的作用。牛磺酸会改善细胞内[Na]i的蓄积以及α-氨基酸的流失。尽管如此，当细胞内牛磺酸含量升高时，会有以下益处：肌浆网释放Ca2+增加、收缩蛋白对Ca2+的敏感性增加，以及与牛磺酸对离子通道作用相关的动作电位可能发生变化。事实上，细胞内应用牛磺酸产生的作用与细胞外给予该氨基酸产生的作用相反。根据我们之前的实验，牛磺酸对心肌细胞的电生理作用如下：(a) 在高[Ca]i时延长动作电位时程（APD），在低[Ca]i时缩短APD。然而，在多细胞制剂中，牛磺酸并不总是能阻止[Ca]o诱导的效应。(b) 在低细胞内和细胞外Ca2+浓度（[Ca]i和[Ca]o）时刺激自发活动，反之亦然。(c) 在高[Ca]i时抑制L型Ca2+电流（ICa(L)），反之亦然。(d) 增强T型Ca2+电流（ICa(T)）。(e) 抑制快速Na+电流（INa）。(f) 增强对TTX不敏感的缓慢Na+电流。(g) 在高[Ca]i时抑制延迟整流K+电流（IKrec），反之亦然。(h) 增强瞬时外向电流（Ito）。(i) 抑制ATP敏感性K+电流（IK(ATP)）。由于牛磺酸作用于如此多的离子通道和转运体，显然它是非特异性的。虽然很难理解牛磺酸作用的多样性，但牛磺酸有可能在低[Ca]i以及Ca2+过载的情况下发挥其强大的心脏保护作用。因此，尽管牛磺酸诱导的对位于心肌细胞膜上的离子通道的调节很复杂，但多种效应可能共同产生有益的治疗效果。
