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The origin of (+)‐tubocurarine resistance in dystrophic mice
Author(s) -
Kelly S.S.,
Morgan G.P.,
Smith J.W.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb11119.x
Subject(s) - curare , chemistry , medicine , endocrinology , anatomy , biology , anesthesia
1 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). 2 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 IC 50 (concentration producing 50% inhibition of stimulus‐evoked contractions) values for the curare block of muscle twitch were 0.78 ± 0.03 μM and 1.32 ± 0.05 μM (mean ± 95% confidence limits) for muscles from normal and dystrophic mice, respectively. 3 There was no difference between muscles from normal and dystrophic mice in the number of α‐bungarotoxin binding sites per endplate. 4 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 μM 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. 5 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. 6 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.