The Mechanochemistry of Muscular Contraction

Abstract

The dependence of PC1 and ATP1 dephosphorylation on the number of isometric twitches in the iodoacetate-nitrogen-poisoned muscle has been examined. There is no net dephosphorylation of adenosinetriphosphate. PC dephosphorylation varies linearly with the number of twitches and produces equivalent amounts of C1 and P1i.1 Iodoacetate concentrations which block the enzyme, creatine phosphokinase, render the muscle non-contractile. A value of 0.286 µmole/gm. for the amount of PC split per twitch is obtained which gives a value of -9.62 kcal./mole for the "physiological" heat of hydrolysis of PC in agreement with expectations based on thermochemical data. In a single maximal isometric twitch it is estimated that 2 to 3 PC molecules are dephosphorylated per myosin molecule, or 1 per actin molecule. The results support the view that under the conditions of these experiments PC dephosphorylation is the net energy yielding reaction. The in vivo stoichiometry of the mechano-chemistry of contraction revealed by these studies on the one hand, and the known stoichiometry of actin polymerization and its coupling to the creatine phosphokinase system on the other are strikingly similar and strongly suggest that the reversible polymerization of actin is involved in a major way in the contraction-relaxation-recovery cycle of muscle.

Separate measures of ATP utilization and recovery in human skeletal muscle.

“…Thus for a range of stimulations used in our experiments, the forearm musculature operated far from its maximal ATPase rate as expected with unfused twitch stimulation. Figure 10 shows that the PCr breakdown slope increased linearly with stimulation frequency from 0 5 to 2 Hz, indicating a constant energy use per twitch as found for frog skeletal muscle (Carlson & Siger, 1960). This measure of contractile cost reflects the underlying economy of contraction, which is low for fast-twitch fibres and high for slow-twitch fibres (Crow & Kushmerick, 1982;Rall, 1985).…”

The Mechanochemistry of Cardiac Muscle

“…The mean maximal active tension generated by these muscles was 3.6 0.2 g/mm 2 . This was slightly less than the mean maximal active tension (5.1 0.3 g/mm2) generated by these same muscles at the end of the equilibration period.…”

“…The energy utilization of 0.12 mole CP/g is compared to that of Ricchiuti and Gibbs in which the heat equivalent of 0.14 #mole CP/g was used in an isometric contraction of approximately 4.7 g/mm 2 .…”

“…While the thermodynamics of skeletal muscle have been investigated with heat measurements for half a century (1), it is only in the past decade that information on the chemical energetics of skeletal muscle has been obtained (2)(3)(4)(5)(6). The first extension of heat measurements to cardiac muscle in vitro has been made in the past year by Ricchiuti and Gibbs (7).…”

Post-contractile phosphocreatine splitting in muscle as revealed by time-resolved 31P nuclear magnetic resonance.

“…These changes recover after relaxation, if oxygenation is adequate. This has been revealed by chemical analysis (LUNDSGAARD, 1934;CARLSON and SIGER, 1960;MOMMAERTS, 1969;CURTIN and WOLEDGE, 1978;HOMSHER and KEAN, 1978) and by phosphorus nuclear magnetic resonance (31P NMR) of living muscle (DAWSON et al, 1977). Improved time-resolution of 31P NMR has allowed us to follow the course of changes of the levels of PCr and P; associated with contraction of living muscles in more detail and without the confusing intervention of semi-specific metabolic inhibitors such as iodoacetate (IAA) or fluorodinitrobenzene (FDNB).…”