Abstract
The influence of moderately elevated extracellular potassium concentration ([K+]) on muscle force has marked similarities to that of posttetanic potentiation (PTP) in that twitch force may be enhanced whilst high-frequency force is depressed. The purpose of this work was to test whether K+-induced potentiation is mechanistically related to PTP via skeletal myosin light-chain kinase (skMLCK)-catalyzed phosphorylation of the myosin regulatory light chains (RLC). To do this, we assessed the influence of elevated [K+] on the force response at various frequencies in extensor digitorum longus (EDL) muscles isolated from wild-type and skeletal myosin light-chain kinase (skMLCK−/−) absent mice. Changing [K+] of the incubation medium from 5 to 10 mmol increased isometric twitch force by a similar amount in wild-type and skMLCK−/− muscles (~ 13% in both genotypes) (all data n = 7–8, P < 0.05). In contrast, 100- and 200-Hz forces were depressed in both genotypes (by 5–7 and 15–18%, respectively). The isometric twitch potentiation caused by a tetanic stimulus series was similar at both [K+] levels for each genotype but was much greater for wild-type than for skMLCK−/− muscles (i.e., 23–25 and 8–9%, respectively). Thus, we conclude that [K+]- and stimulation-induced potentiation are additive and that [K+]-induced potentiation is independent of RLC phosphorylation.
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The authors thank Val Andrew Fajardo for valuable guidance and methodological input and Sebastian Silvera for technical assistance.
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Kristian Overgaard and Rene Vandenboom contributed to the study conception and design. All authors contributed to data collection and analysis and to writing and commenting on previous versions of the manuscript. All authors read and approved the final manuscript.
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Overgaard, K., Gittings, W. & Vandenboom, R. Potentiation of force by extracellular potassium and posttetanic potentiation are additive in mouse fast-twitch muscle in vitro. Pflugers Arch - Eur J Physiol 474, 637–646 (2022). https://doi.org/10.1007/s00424-022-02681-z
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DOI: https://doi.org/10.1007/s00424-022-02681-z