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Model of skeletal muscle cramp and its reversal

K Tasaki , P J Noble , A Garny , P R Shorten , D Noble

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This is an example of a letter article. In an accompanying paper (Noble et al., 2019), we developed the Shorten et al. (2007) 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 modelled. 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 can 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.