Effects of 2,3-butanedione monoxime on the contractile activation properties of fast- and slow-twitch rat muscle fibres.
1. The effects of 2,3-butanedione monoxime (BDM, 0.2-10 mmol/l) have been examined at different temperatures on calcium transients (measured with aequorin) and isometric force in intact bundles of fibres from soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles of the rat and on Ca2+-activated isometric force of mechanically skinned soleus and EDL fibres. Ca2+ release and uptake by the sarcoplasmic reticulum has also been investigated directly on skinned EDL fibres at 1 mmol/l BDM at 23 degrees C. 2. BDM bound calcium with low affinity (KCaBDMapp = 55.9 +/- 4.3 M-1 at 22 degrees C, pH 7.10, ionic strength approximately 155 mmol/l) and did not affect the kinetics and quantum yield of the Ca2+-induced aequorin luminescence. 3. BDM reversibly reduced both force- and Ca2+-dependent aequorin light during the twitch and tetanus of all intact-muscle preparations in a dose-related manner. Twitch responses of soleus fibres were more sensitive to BDM than were EDL fibres. Higher concentrations of BDM were needed to abolish the tetanic force response than the twitch response in both muscle types. 4. The initial rate of rise and the decay rate constants of twitches in both soleus and EDL muscles were increased in the presence of BDM. Accordingly, a higher frequency of stimulation was required to produce fusion of the tetanus. This phenomenon could be explained by the reduced magnitude of the Ca2+ transient. 5. BDM reduced maximal Ca2+-activated force development in mechanically skinned soleus and EDL muscle fibres in a dose-dependent fashion. This depression of force was less sensitive to BDM than were the light transients in intact fibres. Furthermore, BDM affected EDL skinned fibres to a greater extent than soleus skinned fibres, in contrast with its effects on intact fibres. 6. At concentrations of BDM greater than 2.5 mmol/l, BDM significantly decreased the sensitivity of the contractile apparatus to calcium. The relative force-pCa (= -log [Ca2+]) curves for both soleus and EDL skinned fibres were shifted to the right (i.e. to higher calcium concentrations) in a dose-related manner. 7. BDM (10 mmol/l) slowed maximal Ca2+-activated force development of skinned preparations of both fibre types at all temperatures investigated (4-24 degrees C). 8. BDM reduced stiffness in skinned preparations maximally activated by calcium in proportion to the reduction in the isometric force response. BDM also inhibited rigor force of all fibres but only if it was present before the onset of rigor.(ABSTRACT TRUNCATED AT 400 WORDS)
Fryer
M W
MW
Department of Physiology and Pharmacology, University of New South Wales, Kensington, Australia.
Neering
I R
IR
Stephenson
D G
DG
D000331:Aequorin; D000818:Animals; D001696:Biomechanical Phenomena; D002074:Butanones / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003931:Diacetyl / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007537:Isometric Contraction; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002074:Butanones; D000331:Aequorin; D003931:Diacetyl; D002118:Calcium