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- W1976382241 abstract "One of the more difficult questions raised by our students is: “What purpose does bronchoconstriction serve? What is its evolutionary advantage?” The most common answer is that narrowing of the airways increases air velocity and shear, thus facilitating removal of materials in the lumen during cough. From a simplistic point of view, it is difficult to see how under other circumstances sustained bronchoconstriction can be anything but detrimental. This differs from vascular smooth muscle (VSM), where sustained vasoconstriction regulates tissue blood flow. Therefore, it should not be surprising if there are qualitative differences in the mechanisms underlying constriction in smooth muscles subserving different functions. In many cases, application of findings in VSM to the airways may not be appropriate, and could be misleading 1. Considering the prevalence and importance of asthma, however, the number of studies on the contractile mechanisms of airway smooth muscle (ASM) is far fewer than for VSM.One area where investigations in ASM lag behind those in VSM concerns the control of Ca2+ sensitivity of the contractile apparatus. This is despite its potential relevance to asthma, as increased Ca2+ sensitivity may at least partly underlie hyperresponsiveness 2–4. Various factors affect the relationship between intracellular [Ca2+] ([Ca2+]i) and force generation, including modulation of mechanical plasticity 5, but within the contractile apparatus the major determinant is the balance between myosin light chain kinase (MLCK)-dependent phosphorylation of myosin light chain (MLC), and its dephosphorylation by MLC phosphatase (MLCP). It is currently believed that MLCP is primarily regulated via Rho kinase-mediated phosphorylation of its targeting sub-unit MYPT1, and protein kinase C (PKC)- and/or Rho kinase-mediated phosphorylation of the MLCP inhibitor CPI-17; both inhibit MLCP activity and increase Ca2+ sensitivity 4. Agonists increase Ca2+ sensitivity via …" @default.
- W1976382241 created "2016-06-24" @default.
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- W1976382241 date "2006-10-01" @default.
- W1976382241 modified "2023-10-14" @default.
- W1976382241 title "On Ca2+ sensitivity and the airways: not just any smooth muscle" @default.
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- W1976382241 doi "https://doi.org/10.1183/09031936.06.00099406" @default.
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