Length-dependent regulation of basal myosin phosphorylation and force in detrusor smooth muscle

Abstract

Urinary bladder (detrusor) smooth muscle is active in the absence of an external stimulus. Tone occurs even “at rest” during the filling phase, and it is elevated in patients with overactive bladder. This study examined the role of muscle length on tone and the level of basal myosin light chain phosphorylation (MLC20P). MLC20P was 23.9 ± 1% ( n = 58) at short lengths (zero preload; L z). An increase in length from L z to the optimal length for contraction ( L o) caused a reduction in MLC20P to 15.8 ± 1% ( n = 49). Whereas 10 μM staurosporine reduced MLC20P at L z, 1 μM staurosporine, a Ca2+-free solution, and inhibitors of MLC kinase, protein kinase C (PKC) and RhoA kinase (ROK) did not. However, 1 μM staurosporine and inhibitors of ROK inhibited MLC20P and tone at L o. These data support the hypothesis that a Ca2+-independent kinase, possibly ZIP-like kinase, regulates MLC20P at L z, whereas in detrusor stretched to L o, additional kinases, such as ROK, participate.