Modification of the Contractile Properties of Rabbit Skeletal Muscle by Ethylene Glycol1

Abstract

The effect of ethylene glycol on the contractile properties of skeletal muscles was studied using glycerinated rabbit psoas muscle fibers. Measurements were made at an ionic strength of 0.2 M, pH 7.0, and at 10 degrees C. Ethylene glycol reversibly reduced isometric tension, active stiffness, the tension-to-stiffness ratio, and the shortening velocity at zero load (Vo) in a dose-dependent fashion. Ethylene glycol also reduced the Ca sensitivity for contraction. The extent of the reduction in Vo by ethylene glycol was much larger than that in the actomyosin ATPase activity reported by Travers and Hillaire (Eur. J. Biochem. 98, 293-299 [1979]). Although ethylene glycol reduced tension and Vo, the MgATP concentration dependence of these two quantities was almost unaffected. These results suggest that in the presence of ethylene glycol, force produced by crossbridges in the principal force-producing state is reduced and/or the relative population of the attached crossbridges in the low-force state increases. The results also suggest that the reduction in Vo by ethylene glycol is caused not only by a reduction in the actomyosin ATPase activity but also by a reduction in the shortening distance per mole of ATP split.

Dimethyl sulphoxide enhances the effects of Pi in myofibrils and inhibits the activity of rabbit skeletal muscle contractile proteins

“…In contrast with the results with DMSO ( Figure 7A), S1 MgATPase was unaltered by ethylene glycol ( Figure 7B). The data shown for acto-S1 ( Figure 7B) are consistent with earlier studies in which acto-S1 (ATPase) and fibres (contraction velocity) were used [16,27]. 1 µM), and the reaction was started with 5 mM ATP.…”

“…However, a low con-centration of DMSO (1 %, v\v) depressed contraction in isolated skinned fibres of the frog, suggesting a direct effect on the contractile apparatus [35]. In preliminary experiments we found that DMSO, like ethylene glycol [27], also inhibits isometric tension in mammalian skinned fibres, but it can either activate or inhibit the hydrolysis of ATP by myosin in solution, depending on the cation present [36]. Here we have examined the effects of DMSO on the steady-state properties of myosin subfragment 1 (S1), acto-S1, myofibrils and skinned fibres, and in motility assays using acto-heavy meromyosin (HMM).…”

“…The Hill coefficient was unchanged. Maruyama et al [27] reported a decrease of 0.4 pCa unit in 15 % ethylene glycol, a concentration at which the effect on maximal isometric tension was essentially identical with that seen with 10 % DMSO.…”

“…At 15 mC, inhibition was halfmaximal at " 10 % DMSO (1.3 M), and nearly complete at 20 % (Figure 2). With ethylene glycol (at 10 mC), higher concentrations were required : inhibition was half-maximal at 15 % (2.4 M) [27]. Inhibition of tension by DMSO occurred rapidly ( 5 s) and was readily reversible by washing (results not shown).…”

“…It has been particularly valuable in providing access to the very fast reactions involving ATP binding, isomerization and actin dissociation at the beginning of the cycle [20,[23][24][25]. However, ethylene glycol has more complex effects in preparations that contain regulated thin filaments [26][27][28]. Recently, Stehle et al [28] presented evidence to show that ethylene glycol inhibits the formation of strong crossbridges by shifting the thin-filament complex toward the offposition, and not by favouring myosin-nucleotide complexes that bind weakly to actin.…”