Wetzel Petra, Papadopoulos Simon, Gros Gerolf
Zentrum Physiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany, Wetzel.
Pflugers Arch. 2002 Mar;443(5-6):762-70. doi: 10.1007/s00424-001-0777-6. Epub 2002 Jan 22.
Muscle carbonic anhydrase (CA) was inhibited in fibre bundles of the extensor digitorum longus (EDL) and soleus (SOL) muscles from rats. Isometric single twitches were recorded in the absence or presence of the CA inhibitors. The highly membrane-permeable inhibitors L-645,151, chlorzolamide (CLZ) and ethoxzolamide (ETZ) prolonged significantly the values of time-to-peak (ttp) by 5-40 ms (10-40%) in both muscles and the values of the 75% decay time (t(75%)) by 30-400 ms (13-110%) in SOL and by 9-17 ms (15-30%) in EDL and increased peak force by 20--55% in SOL and EDL. The poorly membrane-permeable inhibitors benzolamide (BZ) and acetazolamide (ACTZ) had no effects on single twitches. In CO(2)-free solution, the effects of L-645,151 on ttp, t(75%) and peak force of SOL were reduced drastically. Removal of CO(2) prolonged ttp and t(75%). In skinned fibres, ETZ and CLZ did not increase force production. Intracellular pH (pH(i)) in SOL and EDL fibres was not affected by 30-60 min exposure to CLZ, ETZ or BZ. The results of L-645,151, CLZ and ETZ on ttp, t(75%) and peak force of twitches are consistent with our hypothesis on the role of the sarcoplasmic reticulum (SR) CA. The SR-CA may mediate sufficiently fast buffering and production of H(+) in the SR that is exchanged for Ca(2+) across the SR membrane. We propose that a H(+) buffering and delivery impaired by CA inhibition slows the kinetics of Ca(2+) release and reuptake and, as a result, slows twitch ttp and t(75%). Aspects of this hypothesis await further validation.
大鼠趾长伸肌（EDL）和比目鱼肌（SOL）肌纤维束中的肌肉碳酸酐酶（CA）被抑制。在有无CA抑制剂的情况下记录等长单收缩。高膜通透性抑制剂L-645,151、氯唑胺（CLZ）和乙氧唑胺（ETZ）显著延长了两块肌肉的峰值时间（ttp）值5-40毫秒（10-40%），以及比目鱼肌中75%衰减时间（t(75%)）值30-400毫秒（13-110%），在趾长伸肌中延长了9-17毫秒（15-30%），并使比目鱼肌和趾长伸肌的峰值力增加了20%-55%。低膜通透性抑制剂苯甲酰胺（BZ）和乙酰唑胺（ACTZ）对单收缩无影响。在无CO(2)溶液中，L-645,151对比目鱼肌的ttp、t(75%)和峰值力的影响大幅降低。去除CO(2)延长了ttp和t(75%)。在去表皮纤维中，ETZ和CLZ并未增加力的产生。比目鱼肌和趾长伸肌纤维中的细胞内pH（pH(i)）不受30-60分钟暴露于CLZ、ETZ或BZ的影响。L-645,151、CLZ和ETZ对抽搐的ttp、t(75%)和峰值力的结果与我们关于肌浆网（SR）CA作用的假设一致。SR-CA可能介导肌浆网中足够快的H(+)缓冲和产生，H(+)通过SR膜与Ca(2+)交换。我们提出，CA抑制导致的H(+)缓冲和传递受损会减慢Ca(2+)释放和再摄取的动力学，结果是减慢抽搐的ttp和t(75%)。这一假设的各个方面有待进一步验证。
