Mechanical signals and mechanosensitive modulation of intracellular [Ca2+]in smooth muscle

We tested the hypothesis that strain is the primary mechanical signal in th e mechanosensitive modulation of intracellular Ca2+ concentration ([Ca2+](i )) in airway smooth muscle. We found that [Ca2+](i) was significantly corre lated with muscle length during isotonic shortening against 20% isometric f orce (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-[Ca2+](i) re lationship. Similarly, data points from the 80% F-iso experiments clustered near those from the 50% F-iso experiments. Therefore, despite 2.5- and 4-f old differences in external load, [Ca2+](i) did not deviate much from the l ength-[Ca2+](i) relation that fitted the 20% F-iso data. Maximal inhibition of sarcoplasmic reticular (SR) Ca2+ uptake by 10 mM cyclopiazonic acid (CP A) did not significantly change [Ca2+](i) in carbachol-induced isometric co ntractions and isotonic shortening. CPA also did not significantly change m yosin light-chain phosphorylation or force redevelopment when carbachol-act ivated 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.