Airways in smooth muscle α-actin null mice experience a compensatory mechanism that modulates their contractile response
| Autor: | Aladin M. Boriek, Joan Moore, F. Shardonofsky, Robert J. Schwartz |
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| Rok vydání: | 2012 |
| Předmět: |
Null mice
Physiology Myocytes Smooth Muscle Muscle Proteins Biology Mice Contractile Proteins Airway resistance Smooth muscle Physiology (medical) Animals RNA Messenger Muscle Skeletal Lung Methacholine Chloride Mice Knockout Airway Resistance Contractile response Microfilament Proteins Muscle Smooth Smooth Muscle Myosins Airway smooth muscle respiratory system Respiration Artificial Actins Cell biology Mice Inbred C57BL Immunology Lung elastance Muscle Contraction |
| Zdroj: | Journal of Applied Physiology. 112:898-903 |
| ISSN: | 1522-1601 8750-7587 |
| Popis: | We hypothesized that ablation of smooth muscle α-actin (SM α-A), a contractile-cytoskeletal protein expressed in airway smooth muscle (ASM) cells, abolishes ASM shortening capacity and decreases lung stiffness. In both SM α-A knockout and wild-type (WT) mice, airway resistance (Raw) determined by the forced oscillation technique rose in response to intravenous methacholine (Mch). However, the slope of Raw (cmH2O·ml−1·s) vs. log2Mch dose (μg·kg−1·min−1) was lower ( P = 0.007) in mutant (0.54 ± 0.14) than in WT mice (1.23 ± 0.19). RT-PCR analysis performed on lung tissues confirmed that mutant mice lacked SM α-A mRNA and showed that these mice had robust expressions of both SM γ-A mRNA and skeletal muscle (SKM) α-A mRNA, which were not expressed in WT mice, and an enhanced SM22 mRNA expression relative to that in WT mice. Compared with corresponding spontaneously breathing mice, mechanical ventilation-induced lung mechanical strain increased the expression of SM α-A mRNA in WT lungs; in mutant mice, it augmented the expressions of SM γ-A mRNA and SM22 mRNA and did not alter that of SKM α-A mRNA. In mutant mice, the expression of SM γ-A mRNA in the lung during spontaneous breathing and its enhanced expression following mechanical ventilation are consistent with the likely possibility that in the absence of SM α-A, SM γ-A underwent polymerization and interacted with smooth muscle myosin to produce ASM shortening during cholinergic stimulation. Thus our data are consistent with ASM in mutant mice experiencing compensatory mechanisms that modulated its contractile muscle capacity. |
| Databáze: | OpenAIRE |
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