K+-induced Potentiation And Post-tetanic Potentiation Act Via Independent Mechanisms In Mouse Fast-twitch Muscle

Abstract

A potentiation of force in skeletal muscle has been described as a consequence of moderate increases in extracellular [K+]. This K+-induced potentiation exhibits similarities to the well-described phenomenon of post-tetanic potentiation (PTP), in that both affect force at low frequency of stimulation and that the effect is largest in muscles predominated by fast twitch fibers. Mechanistically PTP is caused largely by skeletal myosin light chain kinase (skMLCK) catalyzed phosphorylation of the myosin regulatory light chains (RLC), while the mechanism of K+-induced potentiation is still not fully elucidated. PURPOSE: To investigate the interactive effects of K+-induced potentiation and PTP and their possible mechanistic overlap between the two potentiation phenomena. METHODS: We assessed the influence of elevated [K+] and PTP on the isometric twitch force response in extensor digitorum longus muscles isolated from wild type and skeletal myosin light chain kinase absent mice (skMLCK-/-). Muscles were incubated in Tyrode solution with either 5 or 10 mM K+ at 25 °C. PTP was elicited by 4 tetanic contractions elicited by brief stimulation trains (0.2-0.4 s at 50-200 Hz) all delivered within 10 s. RESULTS: Increasing [K+] of the incubation medium from 5 to 10 mM increased isometric twitch force by a similar amount in wildtype and skMLCK-/- muscles (~ 12-14 in % both genotypes) (all data n = 7-8, P < 0.05). At 5 mM K+, the relative twitch potentiation caused by a tetanic stimulus series (PTP) was much greater for wildtype than for skMLCK-/- muscles (i.e. 24 and 8%, respectively). In addition, for both genotypes, in muscles already potentiated by 10 mM K+, PTP elicited the same degree of twitch potentiation as that seen at 5 mM K+ (25 and 10% increase in wildtype and skMLCK-/-, respectively). CONCLUSION: We conclude that [K+] and PTP are additive and that [K+]-induced potentiation is independent of RLC phosphorylation.