Rho-Mancing to Sensitize Calcium Signaling for Contraction in the Vasculature: Role of Rho Kinase

T. Szasz, R. C. Webb

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Scopus citations

Abstract

Vascular smooth muscle contraction is an important physiological process contributing to cardiovascular homeostasis. The principal determinant of smooth muscle contraction is the intracellular free Ca2 + concentration, and phosphorylation of myosin light chain (MLC) by activated myosin light chain kinase (MLCK) in response to increased Ca2 + is the main pathway by which vasoconstrictor stimuli induce crossbridge cycling of myosin and actin filaments. A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca2 + concentration, but rather mediating Ca2 + sensitization, is the RhoA/Rho kinase pathway. In response to contractile stimuli, the small GTPase RhoA activates its downstream effector Rho kinase which, in turn, promotes contraction via myosin light chain phosphatase (MLCP) inhibition. RhoA/Rho kinase-mediated MLCP inhibition occurs mainly by phosphorylation and inhibition of MYPT1, the regulatory subunit of MLCP, or by CPI-17-mediated inhibition of the catalytic subunit of MLCP. In this review, we describe the molecular mechanisms underlying the pivotal role exerted by Rho kinase on vascular smooth muscle contraction and discuss the main regulatory pathways for its activity.

Original languageEnglish (US)
Title of host publicationAdvances in Pharmacology
PublisherAcademic Press Inc.
Pages303-322
Number of pages20
DOIs
StatePublished - Jan 1 2017

Publication series

NameAdvances in Pharmacology
Volume78
ISSN (Print)1054-3589
ISSN (Electronic)1557-8925

Keywords

  • Calcium
  • Calcium sensitivity
  • Contractile function
  • Rho
  • Rho kinase
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Pharmacology

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    Szasz, T., & Webb, R. C. (2017). Rho-Mancing to Sensitize Calcium Signaling for Contraction in the Vasculature: Role of Rho Kinase. In Advances in Pharmacology (pp. 303-322). (Advances in Pharmacology; Vol. 78). Academic Press Inc.. https://doi.org/10.1016/bs.apha.2016.09.001