Diabetes mellitus-induced hypersensitivity of mouse skeletal muscles to acetylcholine and succinylcholine.
The myopathy in skeletal muscles of genetically diabetic male KK-CAy mice or alloxan-induced diabetic mice was investigated. In these diabetic mice, nerve-stimulated twitch tensions of in situ sciatic nerve-gastrocnemius muscle preparations were inhibited by intraarterially administered succinylcholine (SuCh) to a greater extent than in normal (non-diabetic) ones. Despite the high blood glucose level, at one week after alloxan administration, no hypersensitivity to SuCh was induced in mice, but mice at 2 weeks and 4 weeks after alloxan showed greater sensitivities. In isolated diaphragm muscles of diabetic KK-CAy mice, the acetylcholine (ACh, iontophoretically applied) potential amplitude was greater than in KK-CAy prediabetic muscles. SuCh in diabetic KK-CAy muscles inhibited ACh potentials to a greater extent than in normal ddY muscles. Hill coefficients obtained from the inhibition curve by SuCh of the nerve-stimulation response were decreased by the diabetic state. The sensitivities to d-tubocurarine and alpha-bungarotoxin were the same in both kinds of muscles. Both extrajunctional ACh receptors in denervated muscles of normal ddY and diabetic KK-CAy mice revealed the lower sensitivity to SuCh than junctional receptors in non-denervated normal muscles. In conclusion, diabetic muscles showed the hypersensitivity restricted to SuCh. These phenomena are neither due to glycosylation nor to denervation supersensitivity.
Kimura
M
M
Kimura
I
I
Nojima
H
H
Muroi
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects*; D009121:Muscle Denervation; D011950:Receptors, Cholinergic / Q000187:drug effects; D013390:Succinylcholine / Q000494:pharmacology*; D014403:Tubocurarine / Q000494:pharmacology
D001786:Blood Glucose; D011950:Receptors, Cholinergic; D013390:Succinylcholine; D000109:Acetylcholine; D014403:Tubocurarine