Increase in electrically-stimulated Ca2+ release and suppression of caffeine response in diaphragm muscle of alloxan-diabetic mice compared with the denervation effect.
Changes in intracellular Ca2+ release in the diaphragm muscle of alloxan-diabetic mice were compared with changes in normal muscles and non-diabetic denervated muscles. We measured Ca2+ transient aequorin luminescence by direct electrical stimulation of these muscles. External Ca2(+)-free solution readily decreased the Ca2+ transient in normal muscles but had less of an effect in diabetic muscles. Only when the muscles were pre-injected with EGTA (reducing intracellular levels of free Ca2+) did the Ca2+ transients decrease significantly in diabetic muscles, however, there was no effect in denervated muscles. The caffeine-induced increase in Ca2+ transients, however, was delayed in both diabetic muscles and non-diabetic denervated muscles. The caffeine response was observed in normal muscles under the external Ca2(+)-free conditions even after EGTA-pretreatment, whereas it was suppressed, after a brief increase, in both diabetic and non-diabetic denervated muscles. These results demonstrate (1) the insensitivity of intracellular Ca2+ mobilization to external Ca2+ levels and the ready accumulation of intracellular Ca2+ in the cytosol in the diabetic state, (2) increased permeability to Ca2+ in the denervated state and (3) impairment of the Ca2+ pool which responds to caffeine in both diabetes and the non-diabetic denervated state. Diabetic neuromyopathy thus appears to be a state of abnormal Ca2(+)-mobilization caused secondarily by high levels of blood glucose.
Kimura
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Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharamceutical University, Japan.
Kimura
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Kimura
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D000331:Aequorin; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003964:Diaphragm; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007700:Kinetics; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D012016:Reference Values
D002110:Caffeine; D000331:Aequorin; D002118:Calcium