Diabetic state-induced rapid inactivation of noncontractile Ca2+ mobilization operated by nicotinic acetylcholine receptor in mouse diaphragm muscle.
1. Diabetic modifications of nicotinic receptor-operated noncontractile Ca2- mobilization observed in the presence of anticholinesterase were investigated by measuring Ca(2+)-aequorin luminescence in diaphragm muscles of mice with diabetes induced by injections of streptozotocin (150 mg kg-1, bolus i.v.) and alloxan (85 mg kg-1, bolus i.v.). 2. The diabetic state accelerated the decline of noncontractile Ca2+ transients without affecting their peak amplitude. Insulin treatment reversed this alteration. 3. The increase in contractile Ca2+ transients by cholinesterase inhibition was attenuated 0.6 fold and became resistant to changes in [Ca2+]o in the diabetic state. 4. Changes in extracellular pH from 7.6 to 5.6 depressed the peak amplitude of noncontractile Ca2+ transients without affecting their duration, and enhanced the peak amplitude of contractile Ca2+ transients. 5. These results suggest that the inactivation process of noncontractile Ca2+ mobilization is promoted in diabetic muscles, presumably by desensitization of the nicotinic acetylcholine receptor.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Tsuneki
H
H
Dezaki
K
K
Kimura
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D016883:Diabetic Ketoacidosis / Q000378:metabolism / Q000503:physiopathology; D003964:Diaphragm / Q000378:metabolism* / Q000648:ultrastructure; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000502:physiology*
D011978:Receptors, Nicotinic; D002118:Calcium