Potentiation of force by extracellular potassium and posttetanic potentiation are additive in mouse fast-twitch muscle in vitro.

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.