The origin of (+)-tubocurarine resistance in dystrophic mice.
Intracellular recording, twitch responses and radio-ligand binding techniques were used to study the causes of resistance to (+)-tubocurarine (curare) of extensor digitorum longus (EDL) muscles from dystrophic mice (129 ReJ/strain). The indirectly evoked twitch response of muscles from dystrophic mice was more resistant to block by curare than the twitch response of muscles from normal littermates. The IC50 (concentration producing 50% inhibition of stimulus-evoked contractions) values for the curare block of muscle twitch were 0.78 +/- 0.03 microM and 1.32 +/- 0.05 microM (mean +/- 95% confidence limits) for muscles from normal and dystrophic mice, respectively. There was no difference between muscles from normal and dystrophic mice in the number of alpha-bungarotoxin binding sites per endplate. The amplitudes of both spontaneous miniature endplate potentials (m.e.p.ps) in unblocked preparations and of evoked endplate potentials (e.p.ps) in 1.91 microM curare were greater in muscles from dystrophic mice than in muscles from normal mice. The ratio dystrophic/normal was greater for the e.p.p. amplitudes than for the m.e.p.p. amplitudes. The quantum content of e.p.ps in magnesium-blocked and in cut-fibre preparations was greater in muscles from dystrophic mice than in muscles from normal littermates. Calculation of the binomial parameters n and p in the cut-fibre preparations indicated that this increased quantum content was caused by an increase in the value of p. It is concluded that at least part of the increased resistance to curare of the indirectly evoked twitch response of muscles from dystrophic mice is due to an increase in the quantum content of e.p.ps in these muscles.
D000818:Animals; D004351:Drug Resistance; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000378:metabolism; D011978:Receptors, Nicotinic; D014403:Tubocurarine / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008274:Magnesium; D014403:Tubocurarine