| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
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
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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
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