Department of Physiology, University of Debrecen, P.O. Box 22, 4012, Debrecen, Hungary.
Pflugers Arch. 2012 Aug;464(2):167-74. doi: 10.1007/s00424-012-1114-y. Epub 2012 May 22.
Tetrodotoxin (TTX) is believed to be the most selective inhibitor of voltage-gated fast Na(+) channels in excitable tissues, including nerve, skeletal muscle, and heart, although TTX sensitivity of the latter is lower than the former by at least three orders of magnitude. In the present study, the TTX sensitivity of L-type Ca(2+) current (I (Ca)) was studied in isolated canine ventricular cells using conventional voltage clamp and action potential voltage clamp techniques. TTX was found to block I (Ca) in a reversible manner without altering inactivation kinetics of I (Ca). Fitting results to the Hill equation, an IC(50) value of 55 ± 2 μM was obtained with a Hill coefficient of unity (1.0 ± s0.04). The current was fully abolished by 1 μM nisoldipine, indicating that it was really I (Ca). Under action potential voltage clamp conditions, the TTX-sensitive current displayed the typical fingerprint of I (Ca), which was absent in the presence of nisoldipine. Stick-and-ball models for Cav1.2 and Nav1.5 channel proteins were constructed to explain the differences observed between action of TTX on cardiac I (Ca) and I (Na). This is the first report demonstrating TTX to interact with L-type calcium current in the heart.
河豚毒素（TTX）被认为是可兴奋组织（包括神经、骨骼肌和心脏）电压门控快速 Na(+) 通道的最选择性抑制剂，尽管 TTX 对后者的敏感性至少低三个数量级。在本研究中，使用常规电压钳和动作电位电压钳技术，在分离的犬心室细胞中研究了 L 型 Ca(2+) 电流（I (Ca)）对 TTX 的敏感性。发现 TTX 以可逆的方式阻断 I (Ca)，而不改变 I (Ca)的失活动力学。根据 Hill 方程拟合结果，得到 IC(50)值为 55±2 μM，Hill 系数为 1.0±s0.04。1 μM 尼卡地平可完全消除电流，表明其确实为 I (Ca)。在动作电位电压钳条件下，TTX 敏感电流显示出 I (Ca)的典型特征指纹，而在尼卡地平存在下则没有。构建 Cav1.2 和 Nav1.5 通道蛋白的棒球模型，以解释 TTX 对心脏 I (Ca)和 I (Na)作用观察到的差异。这是第一个报道证明 TTX 与心脏 L 型钙电流相互作用的报告。
