Role of RhoA/Rho-kinase and Calcium Sensitivity in Airway Smooth Muscle Functions

  • Satoru ItoEmail author


Changes in the contractility of airway smooth muscle (ASM) play important roles in bronchoconstriction and airway hyperresponsiveness associated with the pathophysiology of asthma and possibly, in part, chronic obstructive pulmonary disease (COPD). A common feature associated with ASM contraction is phosphorylation of myosin light chain (MLC), which is determined by the balance between MLC kinase (MLCK) and MLC phosphatase (MLCP) activities. MLCK is activated by increases in the intracellular Ca2+ concentration ([Ca2+]i), whereas MLCP is inactivated by Rho-kinase, a target protein of RhoA, independently of [Ca2+]i. The latter mechanism, contraction due to MLCP inhibition mediated by RhoA/Rho-kinase, is a major type of Ca2+ sensitization. Phosphorylation of the 17-kD myosin phosphatase inhibitor protein by protein kinase C is another mechanism of Ca2+ sensitization via MLCP suppression. This chapter focuses on recent evidence regarding regulation of ASM contraction by the RhoA/Rho-kinase pathway and the possible roles of this pathway in the pathogenesis of asthma and COPD.


Asthma Chronic obstructive pulmonary disease Ca2+ sensitization RhoA Rho-kinase Myosin light chain phosphatase 



airway smooth muscle


intracellular Ca2+ concentration


chronic obstructive pulmonary disease


17-kD myosin phosphatase inhibitor protein


GTPase-activating protein


guanine nucleotide dissociation inhibitor


guanosine diphosphate


guanine nucleotide exchange factor

G protein

GTP-binding protein


guanosine trisphosphate




inositol 1,4,5-trisphosphate


myosin-binding subunit


myosin light chain


myosin light chain kinase


myosin light chain phosphatase


platelet-derived growth factor


protein kinase A


protein kinase C




sphingosine 1-phosphate


sarcoplasmic reticulum




tumor necrosis factor-α


transient receptor potential



This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (17790531, 19689017, and 22590837). We also thank Ms. Katherine Ono for providing language help.


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© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of Respiratory MedicineNagoya University Graduate School of MedicineNagoyaJapan

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