Length-dependent regulation of basal myosin phosphorylation and force in detrusor smooth muscle.
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 (MLC(20P)). MLC(20P) 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 MLC(20P) to 15.8 +/- 1% (n = 49). Whereas 10 microM staurosporine reduced MLC(20P) at L(z), 1 microM staurosporine, a Ca(2+)-free solution, and inhibitors of MLC kinase, protein kinase C (PKC) and RhoA kinase (ROK) did not. However, 1 microM staurosporine and inhibitors of ROK inhibited MLC(20P) and tone at L(o). These data support the hypothesis that a Ca(2+)-independent kinase, possibly ZIP-like kinase, regulates MLC(20P) at L(z), whereas in detrusor stretched to L(o), additional kinases, such as ROK, participate.
Ratz
Paul H
PH
Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501, USA. ratzph@evms.edu
Miner
Amy S
AS
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011817:Rabbits; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D054460:rho-Associated Kinases
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D001285:Atropine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019311:Staurosporine; D002118:Calcium