title: The importance of Rho-associated kinase-induced Ca2+ sensitization as a component of electromechanical and pharmacomechanical coupling in rat ureteric smooth muscle.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK.
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Borysova
authors.forename: S
authors.initials: S
authors.lastname: Shabir
authors.forename: Michael P
authors.initials: MP
authors.lastname: Walsh
authors.forename: Theodor
authors.initials: T
authors.lastname: Burdyga
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D004789:Enzyme Activation; D007668:Kidney / Q000502:physiology; D055595:Mechanical Phenomena; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D014513:Ureter / Q000166:cytology / Q000502:physiology*; D001743:Urinary Bladder / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D018994:Myosin Light Chains; D012965:Sodium Chloride; D002217:Carbachol; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D043263:Myosin-Light-Chain Phosphatase; D002118:Calcium