Diabetic state‐induced rapid inactivation of noncontractile Ca²⁺ mobilization operated by nicotinic acetylcholine receptor in mouse diaphragm muscle

Diabetic modifications of nicotinic receptor‐operated noncontractile Ca²⁺ mobilization observed in the presence of anticholinesterase were investigated by measuring Ca²⁺‐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.). The diabetic state accelerated the decline of noncontractile Ca²⁺ transients without affecting their peak amplitude. Insulin treatment reversed this alteration. 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. 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. These results suggest that the inactivation process of noncontractile Ca²⁺ mobilization is promoted in diabetic muscles, presumably by desensitization of the nicotinic acetylcholine receptor. 1995 British Pharmacological Society