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Ureteric peristalsis, which occurs via alternating contraction and relaxation of ureteric smooth muscle, ensures the unidirectional flow of urine from the kidney to the bladder. Understanding of the molecular mechanisms underlying ureteric excitation-contraction coupling, however, is limited. To address these knowledge deficits, and in particular to test the hypothesis that Ca2+ sensitization via activation of the RhoA/Rho-associated kinase (ROK) pathway plays an important role in ureteric smooth muscle contraction, we carried out a thorough characterization of the electrical activity, Ca2+ signaling, MYPT1 (myosin targeting subunit of myosin light chain phosphatase, MLCP) and myosin regulatory light chain (LC20) phosphorylation, and force responses to membrane depolarization induced by KCl (electromechanical coupling) and carbachol (CCh) (pharmacomechanical coupling). The effects of ROK inhibition on these parameters were investigated. We conclude that the tonic, but not the phasic component of KCl- or CCh-induced ureteric smooth muscle contraction is highly dependent on ROK-catalyzed phosphorylation of MYPT1 at T855, leading to inhibition of MLCP and increased LC20 phosphorylation.

Original publication

DOI

10.1016/j.ceca.2011.07.003

Type

Journal article

Journal

Cell Calcium

Publication Date

10/2011

Volume

50

Pages

393 - 405

Keywords

Action Potentials, Animals, Calcium, Calcium Signaling, Carbachol, Enzyme Activation, Kidney, Mechanical Phenomena, Muscle Contraction, Muscle, Smooth, Myosin Light Chains, Myosin-Light-Chain Phosphatase, Phosphorylation, Protein Phosphatase 1, Rats, Sodium Chloride, Ureter, Urinary Bladder, rho-Associated Kinases