Shortening speed dependent force potentiation is attenuated but not eliminated in skeletal muscles without myosin phosphorylation

Abstract

We investigated the influence of shortening speed on concentric force potentiation at different frequencies in muscles devoid of skeletal myosin light chain kinase (skMLCK^−/−) and unable to phosphorylate myosin. EDL muscles from skMLCK^−/− mice were activated in vitro (25 °C) across a range of stimulation frequencies (10–100 Hz) during shortening ramps at 0.10, 0.30, or 0.50 of maximum shortening velocity (V_max) before and after a potentiating stimulus (PS). When collapsed across all frequencies, the PS increased relative (post/pre) concentric force to 1.27 ± 0.02 and 1.17 ± 0.02 of pre-PS values at 0.50 and 0.30 V_max, respectively (n = 4, P < 0.05 for all speeds). In addition, potentiation was significantly greater at low and intermediate—than at high stimulus frequencies at both speeds. In contrast, during shortening at 0.10 V_max, a posttetanic depression was observed as mean concentric forces were reduced to 0.85 ± 0.02 of pre-PS values. Thus, although reduced compared to published values for wildtype muscles (Gittings et al., J Muscle Res Cell Motil 33:359–368, 2012), skMLCK^−/− muscles displayed a speed dependent potentiation of concentric force during moderate and fast shortening speed at all frequencies tested. Our data support the presence of a myosin phosphorylation—independent mechanism(s) for concentric force potentiation at moderate speeds of shortening, and also suggests that myosin phosphorylation may be necessary to prevent the concentric force depression that may be present at slow speeds of shortening. Although additive in nature, further work is needed to parse out the relative influence of myosin phosphorylation—independent and dependent potentiation mechanisms on wildtype contractile function during dynamic conditions.