The abnormal mobilization of Ca^<2+> and K^+ in diabetic skeletal muscle membranes

为了研究去极化阻滞剂琥珀酰胆碱超敏的原因及其与依赖钙离子的中性蛋白水解酶活性升高的关系，对四氧嘧啶小鼠的横隔肌进行了K^+-和钙离子动员的研究。根据稳态电流-电压(I-V)关系，静息膜电导在糖尿病状态下降低。钾离子通道阻滞剂四乙基铵和钾离子内流抑制剂氯化铯在糖尿病状态下的效果不如正常状态。结论：1.在糖尿病状态下，无氯介质对静息膜电导的降低幅度比正常肌肉大得多。糖尿病状态使钙依赖的慢动作电位的波幅和时程显著降低。无论有无维拉帕米存在，疲劳都会发生，这与正常肌肉对维拉帕米的反应更快地产生疲劳形成相反。利用茶多酚发光技术，检测…的变化比较糖尿病组、非糖尿病失神经组和正常组的细胞内钙离子释放。在外源性无钙溶液作用下，正常肌肉中的钙瞬变现象容易减少，而糖尿病肌肉中钙瞬变的影响较小，只有在肌肉注射EGTA后才能明显降低。EGTA对失神经肌肉的抑制作用不改变其程度。正常肌肉经EGTA处理后，即使在无钙溶液中仍可观察到咖啡因诱导的短暂钙升高，而糖尿病和非糖尿病失神经肌肉在短暂升高后，咖啡因引起的钙瞬变增加。钙调素拮抗剂三氟拉嗪对糖尿病状态下钙瞬变的抑制作用比正常状态下更强。这些结果表明，糖尿病状态导致(1)钾离子电导下降，(2)钙离子内流减少，(3)外部钙离子非依赖性钙离子释放，以及(4)咖啡因依赖的外部钙离子释放。较少

In order to study the cause of supersensitivity for succinylcholine, a depolarizing blocker, and the relation to the increase in the activity of Ca^<2+>-dependent neutral protease, K^+- and Ca^<2+>-mobilization were investigated in diaphragm muscles of alloxan mice.1. Based on steady-state current-voltage (I - V) relationships, resting membrane conductance was decreased by diabetic state. Tetraethylammonium, a K^+channel blocker, and cesium chloride, a K^+ influx inhibitor, became less effective in diabetic state than in normal state. The extent of decrease in resting membrane conductance by C1^--free medium was much greater in diabetic state than in normal muscles.2. Ca^<2+>-dependent slow action potentials were significantly decreased in amplitude and duration by diabetic state. Fatique developed regardless of the presence of verapamil in contrast to the quicker development of fatigue in normal muscles in response to verapamil.3. By the technique of aeguorin luminescence, changes of … More intracellular Ca^<2+> release were compared between diabetic, non-diabetic denervated and normal muscles. By external Ca^<2+>-free solution, Ca^<2+> transient was easily decreased in normal muscles, whereas in diabeic muscles it was less affected and clearly decreased only when the muscles were previously injected with EGTA. The extent of the decreasing effect was not changed by EGTA pretreatment of denervated muscles. The caffeineinduced increase in Ca^<2+> transient was still observed even under the Ca^<2+>-free solution after EGTA pretreatment of normal muscles, whereas it was changed to decreasing effects after the short duration of increase in diabetic and non-diabetic denervated muscles.4. Trifluoperazine, a calmodulin antagonist, suppressed more potently Ca^<2+> transients in diabetic state than in normal state.These results suggest that diabetic state causes (1) K^+ conductance decrease, (2) Ca^<2+> influx decrease, (3) external Ca^<2+>-independent Ca^<2+> release, and (4) external Ca^<2+>-dependent Ca^<2+> release by caffeine. Less