Almers W, Best P M
J Physiol. 1976 Nov;262(3):583-611. doi: 10.1113/jphysiol.1976.sp011611.
The kinetics of mechanical activation of intact fibres were examined with a voltage-clamp technique. Tetracaine (2 mM) increases fifteen- to seventyfold the time required to produce a just visible contraction by cell membrane depolarization. 2. Displacement currents thought to be related to contractile activation remain in 2 mM tetracaine. Their characteristics are virtually identical to those found in the absence of the drug. Displacement currents also remain in fibres immobilized by treatment with 10 mM formaldehyde. 3. Despite its effect on contraction of intact fibres, tetracaine does not diminish contraction tension when Ca is applied directly to the contractile proteins of 'skinned' muscle fibres. The sensitivity of the myofilaments to Ca2+ also remains undiminished. 4. When acting on intact fibres the drug must therefore inhibit Ca2+-release from the sarcoplasmic reticulum. It is estimated that 2 mM tetracaine diminishes more than tenfold the capacity for Ca2+-release in response to cell membrane depolarization.5. If muscle displacement currents represent events linking depolarization to Ca2+-release, then tetracaine must be able to block the release without affecting the potential-sensing portion of the release regulating mechanism. 6. Further experiments on skinned fibres show that tetracaine blocks or greatly diminishes caffeine contractions, but that Cl-induced contractions of normal amplitude are still possible.
采用电压钳技术研究了完整纤维的机械激活动力学。丁卡因（2 mM）使细胞膜去极化产生刚可见收缩所需的时间增加了15至70倍。2. 被认为与收缩激活有关的位移电流在2 mM丁卡因中仍然存在。它们的特性与未使用该药物时几乎相同。在用10 mM甲醛处理固定的纤维中也存在位移电流。3. 尽管丁卡因对完整纤维的收缩有影响，但当直接向“去皮”肌纤维的收缩蛋白施加Ca时，它不会降低收缩张力。肌丝对Ca2+的敏感性也保持不变。4. 因此，当作用于完整纤维时，该药物必定抑制了肌浆网中Ca2+的释放。据估计，2 mM丁卡因使响应细胞膜去极化的Ca2+释放能力降低了十多倍。5. 如果肌肉位移电流代表将去极化与Ca2+释放联系起来的事件，那么丁卡因必定能够阻断释放而不影响释放调节机制的电位传感部分。6. 对去皮纤维的进一步实验表明，丁卡因阻断或大大减弱了咖啡因收缩，但正常幅度的Cl诱导收缩仍然可能。
