Myosin light chain kinase is necessary for tonic airway smooth muscle contraction.
Different interacting signaling modules involving Ca(2+)/calmodulin-dependent myosin light chain kinase, Ca(2+)-independent regulatory light chain phosphorylation, myosin phosphatase inhibition, and actin filament-based proteins are proposed as specific cellular mechanisms involved in the regulation of smooth muscle contraction. However, the relative importance of specific modules is not well defined. By using tamoxifen-activated and smooth muscle-specific knock-out of myosin light chain kinase in mice, we analyzed its role in tonic airway smooth muscle contraction. Knock-out of the kinase in both tracheal and bronchial smooth muscle significantly reduced contraction and myosin phosphorylation responses to K(+)-depolarization and acetylcholine. Kinase-deficient mice lacked bronchial constrictions in normal and asthmatic airways, whereas the asthmatic inflammation response was not affected. These results indicate that myosin light chain kinase acts as a central participant in the contractile signaling module of tonic smooth muscle. Importantly, contractile airway smooth muscles are necessary for physiological and asthmatic airway resistance.
Zhang
Wen-Cheng
WC
Model Animal Research Center of Nanjing University and MOE Key Lab of Model Animal for Disease Study, Nanjing 210061, China.
Peng
Ya-Jing
YJ
Zhang
Gen-Sheng
GS
He
Wei-Qi
WQ
Qiao
Yan-Ning
YN
Dong
Ying-Ying
YY
Gao
Yun-Qian
YQ
Chen
Chen
C
Zhang
Cheng-Hai
CH
Li
Wen
W
Shen
Hua-Hao
HH
Ning
Wen
W
Kamm
Kristine E
KE
Stull
James T
JT
Gao
Xiang
X
Zhu
Min-Sheng
MS
D000109:Acetylcholine / Q000378:metabolism; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001249:Asthma / Q000201:enzymology / Q000235:genetics; D001980:Bronchi / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000201:enzymology*; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014132:Trachea / Q000201:enzymology*
D018931:Antineoplastic Agents, Hormonal; D002147:Calmodulin; D013629:Tamoxifen; D009219:Myosin-Light-Chain Kinase; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium