Paralysis of skeletal muscle by butanedione monoxime, a chemical phosphatase.
The chemical phosphatase butanedione monoxime (BDM) reversibly inhibited twitches and tetanic contractions in bundles of rat soleus fibres in a dose-dependent manner (2-20 mM) but had no effect on the amplitude or time course of action potentials. In addition, BDM reversibly reduced the amplitude of potassium contractures demonstrating a depressant effect on contraction not mediated by action potentials. BDM had no effect on asymmetric charge movement but depressed calcium currents across the surface membrane in voltage-clamped fibres. The most significant effect of BDM on excitation-contraction coupling was a reduction in the amplitude of the calcium transient associated with contraction in aequorin-injected fibres. While these experiments do not eliminate the possibility of a direct effect of BDM on contractile filaments, reduction of calcium release from the sarcoplasmic reticulum, at least at low concentrations of BDM (below 2 mM), would seem to be the main mechanism for the inhibition of contractions in rat skeletal muscle.
Fryer
M W
MW
Department of Physiology and Pharmacology, University of N.S.W., Kensington, Australia.
Gage
P W
PW
Neering
I R
IR
Dulhunty
A F
AF
Lamb
G D
GD
D000331:Aequorin; D000818:Animals; D002074:Butanones / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology*; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000503:physiopathology; D010243:Paralysis / Q000139:chemically induced*; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000187:drug effects
D002074:Butanones; C004717:diacetylmonoxime; D000331:Aequorin; D010744:Phosphoric Monoester Hydrolases; D003931:Diacetyl; D002118:Calcium