Abstract
We tested the hypothesis that strain is the primary mechanical signal in the mechanosensitive modulation of intracellular Ca2+concentration ([Ca2+]i) in airway smooth muscle. We found that [Ca2+]i was significantly correlated with muscle length during isotonic shortening against 20% isometric force (Fiso). When the isotonic load was changed to 50% Fiso, data points from the 20 and 50% Fiso experiments overlapped in the length-[Ca2+]i relationship. Similarly, data points from the 80% Fiso experiments clustered near those from the 50% Fiso experiments. Therefore, despite 2.5- and 4-fold differences in external load, [Ca2+]idid not deviate much from the length-[Ca2+]irelation that fitted the 20% Fiso data. Maximal inhibition of sarcoplasmic reticular (SR) Ca2+ uptake by 10 μM cyclopiazonic acid (CPA) did not significantly change [Ca2+]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 Ca2+ uptake is not the underlying mechanism.