Twitches, tetanic contractions and potassium contractures were recorded isometrically from small bundles of rat soleus muscle fibres. 2. Solutions with reduced calcium concentrations (low-calcium solutions), whether buffered with EGTA (85 and 3 microM-Ca2+) or not (15 microM-Ca2+), caused an initial potentiation of contraction followed by depression. 3. The decay of potassium contractures (200 mM-potassium) was more rapid than normal in low-calcium solutions. 4. Recovery from the inactivation produced by a 200 mM-potassium contracture was slowed in low-calcium solutions but full recovery was seen within 10-15 min after return to a solution containing 2.5 mM-Ca2+. 5. Nifedipine (50 microM) in solutions containing 2.5 mM-Ca2+ potentiated contraction whereas, in low-calcium solutions, contraction was depressed and the depression was more pronounced the lower the Ca2+ concentration. 6. As with low-calcium solutions, potassium contractures decayed more rapidly in solutions containing nifedipine. Nifedipine slowed still further the rate of recovery from inactivation in low-calcium solutions. 7. (-) Bay K 8644 (50 microM) depressed contraction, increased the rate of decay of potassium contractures and slowed recovery from inactivation, like nifedipine. The racemate of Bay K 8644 was less effective. 8. In explanation of these and other observations, it is proposed that there is a dihydropyridine-binding molecule in the walls of the transverse tubular system that normally exists predominantly in a 'precursor' form at the resting membrane potential and is converted by membrane depolarization to an 'activator' form essential for excitation-contraction coupling. Conversion of the precursor to activator involves both conformational change and dissociation of calcium. Prolonged depolarization converts activator to an inactivated form by inducing further conformational change and dissociation of calcium. Recovery from inactivation requires reverse conformational changes and rebinding of calcium. The dihydropyridines affect contraction by reducing the affinity of the molecule for calcium.
摘要
从小鼠比目鱼肌纤维小束上等长记录抽搐、强直收缩和钾挛缩。2. 钙浓度降低的溶液（低钙溶液），无论是否用乙二醇双四乙酸（EGTA，85和3微摩尔/升钙离子）缓冲（15微摩尔/升钙离子），都会引起收缩的初始增强，随后是抑制。3. 在低钙溶液中，钾挛缩（200毫摩尔/升钾）的衰减比正常情况更快。4. 在低钙溶液中，由200毫摩尔/升钾挛缩产生的失活恢复减慢，但在回到含2.5毫摩尔/升钙离子的溶液后10 - 15分钟内可完全恢复。5. 在含2.5毫摩尔/升钙离子的溶液中，硝苯地平（50微摩尔/升）增强收缩，而在低钙溶液中，收缩受到抑制，且钙离子浓度越低，抑制越明显。6. 与低钙溶液一样，在含硝苯地平的溶液中钾挛缩衰减更快。硝苯地平使低钙溶液中失活恢复的速率进一步减慢。7. （-）Bay K 8644（50微摩尔/升）抑制收缩，增加钾挛缩的衰减速率并减慢失活恢复，与硝苯地平相似。Bay K 8644的外消旋体效果较差。8. 为解释这些及其他观察结果，有人提出在横管系统壁中有一个二氢吡啶结合分子，其在静息膜电位时通常主要以“前体”形式存在，通过膜去极化转化为对兴奋 - 收缩偶联至关重要的“激活剂”形式。前体向激活剂的转化涉及构象变化和钙的解离。长时间去极化通过诱导进一步的构象变化和钙的解离将激活剂转化为失活形式。失活恢复需要反向构象变化和钙的重新结合。二氢吡啶通过降低分子对钙的亲和力来影响收缩。
