Tricarico D, Barbieri M, Camerino D C
Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Via Orabona n degrees 4, 70120 Bari, Italy.
Br J Pharmacol. 2000 Jun;130(4):827-34. doi: 10.1038/sj.bjp.0703385.
Taurine is a sulphonic aminoacid present in high amounts in various tissues including cardiac and skeletal muscles showing different properties such as antioxidative, antimyotonic and anti-schaemic effects. The cellular mechanism of action of taurine is under investigation and appears to involve the interaction of the sulphonic aminoacid with several ion channels. Using the patch-clamp technique we studied the effects of taurine in rat skeletal muscle fibres on ATP-sensitive K(+) channel (K(ATP)) immediately after excision and on channels that underwent rundown. The cytoplasmic application of 20 mM of taurine reduced the K(ATP) current; this effect was reverted by washout of the drug solution. In this experimental condition the IC(50) was 20.1 mM. After rundown, taurine inhibited the K(ATP) current with similar efficacy. Competition experiments showed that taurine shifted the dose-response inhibition curve of glybenclamide to the left on the log-dose axis without significantly affecting those of ATP or Ca(2+) ion. Single channel recording revealed that taurine affects the close state of the channel prolonging it and reducing the bursts duration. Our data indicate that taurine inhibits the muscular K(ATP) channel interfering with the glybenclamide site on the sulphonylurea receptor of the channel or on the site allosterically coupled to it. During ischaemia and hypoxia, the skeletal and heart muscles undergo several changes; for example, the activation of K(ATP) channels and loss of the intracellular taurine content. The depletion of taurine during ischaemia would contribute to the early activation of K(ATP) channels and salvage the intracellular ATP content.
牛磺酸是一种磺酸氨基酸，大量存在于包括心肌和骨骼肌在内的各种组织中，具有抗氧化、抗强直性和抗缺血等不同特性。牛磺酸的细胞作用机制正在研究中，似乎涉及这种磺酸氨基酸与几种离子通道的相互作用。我们使用膜片钳技术研究了牛磺酸对大鼠骨骼肌纤维中ATP敏感性钾通道（K(ATP)）在切除后立即以及对发生功能衰退的通道的影响。胞质施加20 mM牛磺酸可降低K(ATP)电流；通过冲洗药物溶液可逆转这种作用。在这种实验条件下，半数抑制浓度（IC(50)）为20.1 mM。功能衰退后，牛磺酸以相似的效力抑制K(ATP)电流。竞争实验表明，牛磺酸使格列本脲的剂量-反应抑制曲线在对数剂量轴上向左移动，而对ATP或Ca(2+)离子的曲线没有显著影响。单通道记录显示，牛磺酸影响通道的关闭状态，延长关闭时间并缩短爆发持续时间。我们的数据表明，牛磺酸抑制肌肉K(ATP)通道，干扰通道磺脲类受体上的格列本脲位点或与其变构偶联的位点。在缺血和缺氧期间，骨骼肌和心肌会发生多种变化；例如，K(ATP)通道的激活和细胞内牛磺酸含量的丧失。缺血期间牛磺酸的消耗会导致K(ATP)通道的早期激活，并挽救细胞内ATP含量。
