Miledi R, Parker I, Zhu P H
J Physiol. 1984 Jun;351:687-710. doi: 10.1113/jphysiol.1984.sp015271.
Intracellular calcium transients were recorded from voltage-clamped frog twitch muscle fibres using Arsenazo III. The possible role of extracellular ions in excitation-contraction (e.-c.) coupling was examined using ion substitutions and blocking drugs in the bathing medium. Parameters measured included the Arsenazo response size to a standard depolarizing pulse (5 ms, 0 mV) and the strength-duration curve for threshold Arsenazo signal. Addition of tetrodotoxin (TTX) decreased the response size to small (-30 mV, 5 ms), but not large (+30 mV, 10 ms) depolarizations, probably because of poor voltage clamp of the tubular membrane in the absence of TTX. Clamping TTX-treated fibres with the wave form of a recorded action potential gave an Arsenazo response similar to that elicited by the normal action potential (at 10 degrees C). Complete substitution of sodium (by choline, lithium or Tris) or chloride (by methyl sulphate or maleate) in the bathing solution gave no appreciable changes in the size of the Arsenazo response. Reduction of extracellular free [Ca2+] to low levels using EGTA caused a slight reduction in the calcium signal elicited by the standard depolarization (to 74% after a few hours, and to 62% after 2 days; temperature 5-10 degrees C). The strength-duration curve was unchanged. Arsenazo responses about 75% of the control size could be elicited in high potassium solution (42 mM-K2SO4) by strong (+80 mV, 20 ms) depolarizations, after re-polarizing the fibres to -90 mV for a few minutes. The voltage dependence of activation was shifted to more positive potentials in this solution. Tetraethylammonium (TEA) bromide at a concentration of 20 mM did not alter the Arsenazo signal, whilst 120 mM-TEA reduced the response by 25%. 3,4-diaminopyridine (DAP) reduced the size of the Arsenazo signal at a concentration of 5 mM, and caused spontaneous release of calcium from the sarcoplasmic reticulum (s.r.) in the absence of membrane potential changes. The Arsenazo signal elicited by an action potential was enhanced by 1 mM-DAP, because of prolongation of the action potential, but was depressed by higher concentrations. We conclude that e.-c. coupling does not involve the influx of any external ions into the muscle fibre. If a current flow between the T-tubules and the s.r. is involved in e.-c. coupling, then this is probably carried by an efflux of potassium ions.
使用偶氮胂III从电压钳制的青蛙抽搐肌纤维记录细胞内钙瞬变。在灌流介质中使用离子置换和阻断药物研究了细胞外离子在兴奋-收缩(e.-c.)偶联中的可能作用。测量的参数包括偶氮胂对标准去极化脉冲(5毫秒,0毫伏)的反应大小以及阈值偶氮胂信号的强度-时间曲线。添加河豚毒素(TTX)可降低对小的(-30毫伏,5毫秒)去极化的反应大小,但对大的(+30毫伏,10毫秒)去极化反应大小无影响,这可能是因为在没有TTX的情况下管状膜的电压钳制不佳。用记录的动作电位波形钳制经TTX处理的纤维,得到的偶氮胂反应与正常动作电位(在10℃时)引起的反应相似。在灌流溶液中完全用胆碱、锂或三羟甲基氨基甲烷替代钠或用甲硫酸盐或马来酸盐替代氯,偶氮胂反应大小无明显变化。使用乙二醇双四乙酸(EGTA)将细胞外游离[Ca2+]降低到低水平,导致标准去极化引起的钙信号略有降低(几小时后降至74%,2天后降至62%;温度5 - 10℃)。强度-时间曲线未改变。在高钾溶液(42 mM - K2SO4)中,在将纤维再极化至-90毫伏几分钟后,通过强的(+80毫伏,20毫秒)去极化可引发约为对照大小75%的偶氮胂反应。在此溶液中,激活的电压依赖性向更正的电位移动。浓度为20 mM的溴化四乙铵(TEA)不改变偶氮胂信号,而120 mM - TEA使反应降低25%。浓度为5 mM的3,4 - 二氨基吡啶(DAP)降低偶氮胂信号大小,并在无膜电位变化的情况下引起肌浆网(s.r.)中钙的自发释放。1 mM - DAP由于动作电位延长而增强动作电位引发的偶氮胂信号,但更高浓度时则使其降低。我们得出结论,e.-c.偶联不涉及任何外部离子流入肌纤维。如果T小管和s.r.之间的电流流动参与e.-c.偶联,那么这可能是由钾离子外流介导的。