Tricarico D, Barbieri M, Conte Camerino D
Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Bari, Italy.
J Pharmacol Exp Ther. 2001 Sep;298(3):1167-71.
Emerging evidence supports the idea that taurine exerts some of its actions through inhibition of inward rectifier K(+) channels, ATP-sensitive K(+) channels, and voltage-dependent K(+) channels. However, to date not much is known about the effects of this sulfonic amino acid on Ca(2+)-activated K(+) (K(Ca(2+))) channels, which are widely expressed in various tissues, including skeletal muscle. In the present work, the effects of taurine on K(Ca(2+)) channels of rat skeletal muscle fibers were investigated using the patch-clamp technique. The application of the amino acid to the internal side of the excised macropatches induced a dose-dependent decrease in the outward K(Ca(2+)) currents recorded at positive membrane potentials in the presence of 8 to 16 microM concentrations of free Ca(2+) ions in the bath with an IC(50) of 31.9. 10(-3) +/- 1 M (slope factor = 1.2) (n = 11 patches). In contrast, at negative membrane potentials taurine caused an enhancement of the muscular inward K(Ca(2+)) currents with a DE(50) (drug concentration needed to enhance the current by 50%) of 46.7. 10(-3) +/- 2 M (slope factor = 1.3) (n = 9 patches). Single channel analysis revealed that this effect was mediated by changes in the reversal potential of the K(Ca(2+)) channel for K(+) ions with no changes in the gating properties or in the sensitivity of the channel to Ca(2+) ions. Taurine also did not affect the single channel conductance. In conclusion, taurine shows a voltage-dependent dualistic action on K(Ca(2+)) channels, being an inhibitor of the channel at positive membrane potentials and an activator at negative membrane potentials.
新出现的证据支持这样一种观点,即牛磺酸通过抑制内向整流钾通道、ATP敏感性钾通道和电压依赖性钾通道发挥其部分作用。然而,迄今为止,关于这种磺酸氨基酸对钙激活钾(K(Ca(2+)))通道的影响知之甚少,该通道在包括骨骼肌在内的各种组织中广泛表达。在本研究中,使用膜片钳技术研究了牛磺酸对大鼠骨骼肌纤维K(Ca(2+))通道的影响。将该氨基酸应用于切除的大膜片内侧,在浴液中存在8至16微摩尔浓度的游离钙离子时,在正膜电位下记录到的外向K(Ca(2+))电流呈剂量依赖性降低,半数抑制浓度(IC(50))为31.9×10(-3)±1摩尔(斜率因子 = 1.2)(n = 11个膜片)。相反,在负膜电位下,牛磺酸使肌肉内向K(Ca(2+))电流增强,半数效应浓度(DE(50))(使电流增强50%所需的药物浓度)为46.7×10(-3)±2摩尔(斜率因子 = 1.3)(n = 9个膜片)。单通道分析表明,这种效应是由K(Ca(2+))通道对钾离子的反转电位变化介导的,通道的门控特性或对钙离子的敏感性没有变化。牛磺酸也不影响单通道电导。总之,牛磺酸对K(Ca(2+))通道表现出电压依赖性二元作用,在正膜电位下是通道的抑制剂,在负膜电位下是激活剂。