Mechanical signals and mechanosensitive modulation of intracellular [Ca(2+)] in smooth muscle.
We tested the hypothesis that strain is the primary mechanical signal in the mechanosensitive modulation of intracellular Ca(2+) concentration ([Ca(2+)](i)) in airway smooth muscle. We found that [Ca(2+)](i) was significantly correlated with muscle length during isotonic shortening against 20% isometric force (F(iso)). When the isotonic load was changed to 50% F(iso), data points from the 20 and 50% F(iso) experiments overlapped in the length-[Ca(2+)](i) relationship. Similarly, data points from the 80% F(iso) experiments clustered near those from the 50% F(iso) experiments. Therefore, despite 2.5- and 4-fold differences in external load, [Ca(2+)](i) did not deviate much from the length-[Ca(2+)](i) relation that fitted the 20% F(iso) data. Maximal inhibition of sarcoplasmic reticular (SR) Ca(2+) uptake by 10 microM cyclopiazonic acid (CPA) did not significantly change [Ca(2+)](i) in carbachol-induced isometric contractions and isotonic shortening. CPA also did not significantly change myosin light-chain phosphorylation or force redevelopment when carbachol-activated muscle strips were quickly released from optimal length (L(o)) to 0.5 L(o). These results are consistent with the hypothesis and suggest that SR Ca(2+) uptake is not the underlying mechanism.
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Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D007537:Isometric Contraction / Q000187:drug effects; D007551:Isotonic Contraction / Q000187:drug effects; D008465:Mechanoreceptors / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009218:Myosins / Q000378:metabolism; D009994:Osmolar Concentration; D010766:Phosphorylation; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D013997:Time Factors; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D007211:Indoles; D002217:Carbachol; D009218:Myosins; D002118:Calcium; C000543:cyclopiazonic acid