Changes of intracellular milieu with fatigue or hypoxia depress contraction of skinned rabbit skeletal and cardiac muscle.

Abstract

SUMMARY1. Maximal calcium-activated force (Fmax) and calcium sensitivity were markedly decreased in detergent-skinned fibres from skeletal and cardiac muscle by solutions that mimicked the total milieu changes associated with fatigue and hypoxia. Further experiments determined the relative contribution of each of the individual changes in milieu.2. Both Ca21 sensitivity and Fmax of skeletal and cardiac fibres were decreased with increased [H+] or inorganic phosphate (Pi). These effects were greater in cardiac muscle.3. Decreasing MgATP over the range observed with fatigue and hypoxia (6-18-4-7 mM) had no effect on Fmax or Ca2" sensitivity of either muscle type. 4. Decreasing phosphocreatine (PCr: 15-1 mM) increased Fmax but had little effect on Ca2" sensitivity in both muscle types. In cardiac fibres, the effect on Fmax could be mimicked by inhibition of endogenous creatine kinase.5. ADP (0-7 mm) increased Fmax and Ca21 sensitivity, while AMP (0-06 mM) slightly increased Fmax but had no effect on Ca2" sensitivity of either skeletal or cardiac fibres.6. Creatine (25 mM) had no significant effect on either Ca2" sensitivity or Fmax of skeletal and cardiac muscle fibres. At higher levels (50 mM), however, creatine depressed Fmax and slightly altered Ca2" sensitivity.7. Thiophosphorylation of myosin P light chains (phosphorylatable light chains of myosin) in rabbit psoas fibres had no effect on Ca21 sensitivity, yet slightly but significantly increased Fmax under fatigue conditions. 8. Reducing the affinity for ATP hydrolysis (by adding ADP, AMP and creatine) over the range calculated for fatigue/hypoxia (60-45 kJ/mol) produced the enhancement in Fmax expected from added ADP and AMP in cardiac but not skeletal muscle, indicating that changes in affinity influence Fmax of skeletal muscle. Reducing affinity produced little change in Ca21 sensitivity of skeletal muscle. In contrast, the change produced in cardiac muscle was greater than that expected from addition of ADP and AMP; i.e. decreasing affinity increases calcium sensitivity of the heart. 9. Simple summation of all significant changes expected from each constituent R. E. GODT AND T. M. NOSEK altered by fatigue/hypoxia adequately predicted the observed changes in F... and Ca2+ sensitivity in both cardiac and skeletal muscle fibres with but one exception (the change in Ca2+ sensitivity of skeletal muscle at pH 7 was slightly overestimated).

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

“…Concentrations of fast isoforms of myosin regulatory light chains (MLC) and, in particular, of the regulatory phosphorylatable isoforms known to modulate the rate of force development and of twitch maximal force at different initial tension levels [81][82][83], both of which are relevant to muscle function, were decreased. In vitro phosphorylation of MLC is known to increase calcium sensitivity thereby controlling the rate of force development and maximal force [84]. The drop of phosphorylatable isoforms and the decrement of phosphorylation of the acidic MLC f isoform found in elderly subjects, could impair performance.…”

Continuous fluorimetric assessment of the changes in cytoplasmic calcium concentration during exposure of rat isolated myocardium to conditions of simulated ischaemia

“…[Ca], (Godt & Nosek, 1989). Stern et al (1988), on the other hand, concluded that failure of systolic shortening during SI is accounted for mainly by a loss of the systolic increments in [Ca],.…”

Effect of oral administration of sodium bicarbonate on surface EMG activity during repeated cycling sprints

“…Since glycolysis contributes to the energy supply during a short-term (6-10 s) cycling sprint (Gaitanos et al 1993;Nevill et al 1996), and in repeated cycling sprints (RCS), lactic acid accumulates within muscle, resulting in an increase in hydrogen ions (H + ) within muscle. The reduced intramuscular pH due to intramuscular accumulation of H + had been reported to decrease power output through impairment of the muscle contractile apparatus (Cooke et al 1988; Godt and Nosek 1989). However, a recent study using mammalian skinned muscle fibers (Pate et al 1995) has shown that the reduced intramuscular pH does not adversely affect the muscle contractile apparatus at physiological temperatures.…”