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

糖尿病骨骼肌膜Ca^2和K^的异常动员

基本信息

批准号：
61571093
负责人：
KIMURA Ikuko
金额：
$ 1.47万
依托单位：
Toyama Medical & Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

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

为了研究去极化阻断剂琥珀胆碱超敏性的原因以及与Ca^2+依赖性中性蛋白酶活性增加的关系，对K^+-和Ca^2+-动员进行了研究。在四氧嘧啶小鼠的膈肌中进行了研究。1.根据稳态电流-电压（I - V）关系，糖尿病状态下静息膜电导降低。四乙铵（一种 K^+ 通道阻滞剂）和氯化铯（一种 K^+ 内流抑制剂）在糖尿病状态下的效果低于正常状态。无 C1^- 培养基导致的静息膜电导降低程度要大得多。与正常肌肉相比，糖尿病状态下的慢动作电位显着降低。相比之下，无论是否存在维拉帕米，糖尿病状态下的疲劳都会显着降低。正常肌肉对维拉帕米的反应更快地产生疲劳。3.通过白蛋白发光技术，比较了糖尿病、非糖尿病去神经和正常肌肉之间细胞内 Ca^<2+> 释放的变化。无Ca^2+溶液，Ca^2+瞬变在正常肌肉中很容易降低，而在糖尿病肌肉中，其影响较小并且仅当肌肉预先注射EGTA时才明显降低。去神经肌肉的EGTA预处理没有改变降低效果的程度，在正常肌肉的EGTA预处理后，即使在不含Ca 2+ 的溶液中仍然观察到咖啡因诱导的Ca 2+ 瞬时增加。在糖尿病和非糖尿病去神经肌肉的短期增加后，三氟拉嗪（一种钙调蛋白拮抗剂）更有效地抑制Ca ^ 2+ 瞬变。这些结果表明，糖尿病状态导致（1）K^+电导降低，（2）Ca^<2+>流入减少，（3）外部Ca^<2+>独立Ca^< 2+>释放，以及(4)咖啡因外部Ca^<2+>依赖性Ca^<2+>释放。