Abstract
In an accompanying paper [2], we developed the Shorten [3] model of skeletal muscle by incorporating equations such as surface calcium fluxes. In further research in this paper, we succeeded in reproducing muscle cramp, as well as its prevention and reversal, by investigating muscle contraction and cramp, in which calcium regulatory networks are involved, using the extended model in comparison with the original model. Incorporation of data from a traditional medicine from root extracts of paeony and licorice and one of its pure chemicals was modeled. The sensitivity analysis of the extended model shows the robustness of the calcium regulatory networks. Muscle cramp, in the extended model, requires calcium influx via the L-type calcium channel and it will not occur without calcium influx. Reduced calcium influx can delay or prevent cramp. Increased interstitial potassium is implicated in developing and maintaining cramp. Mechanism of reversal of cramp requires wash-out of extracellular potassium via increased blood flow, followed by calcium efflux via sodium-calcium exchange. This paper shows the first successful quantitative electrophysiological and mechanical model of cramp and of its reversal.
Highlights
Purpose of development of the original modelBoth fatigue and cramp are important pathologies of skeletal muscle
It is difficult to account for the development of muscle cramp without supposing that calcium influx may be important
Supporting experimental data showing why sarcolemmal calcium transporters need to be incorporated For interaction with this modelling research, we use some of the experimental data performed in the Oxford laboratories on a 1:1 combination of root extracts from peony and licorice and one of its pure chemicals, glycyrrhetinic acid (GA)
Summary
The Shorten et alShorten et al (2007) model reproduces muscle fatigue, but not muscle cramp. The latter is incapacitating and often painful. The prevalence of muscle cramp in patients with muscle cramp over the age of 60 is around 46% (Maisonneuve et al, 2016), with a high impact on quality of life: 21% of sufferers “described their symptoms as very distressing”. It is a widespread health problem in aging populations. Overloading the muscle fibres with calcium might satisfy this criterion since it would maintain contraction for as long as the free intracellular calcium is above the threshold for activating the cross-bridge reactions of the contractile proteins
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