Selected Contribution: Roles of focal adhesion kinase and paxillin in the mechanosensitive regulation of myosin phosphorylation in smooth muscle. Tang, Dale D., and Susan J. Gunst. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202
APStracts 8:0321A, 2001.
The increase in intracellular Ca2+ and myosin light chain (MLC) phosphorylation in response to the contractile activation of tracheal smooth muscle is greater at longer muscle lengths (21). However, MLC phosphorylation can also be stimulated by Ca2+- insensitive signaling pathways (19). The cytoskeletal proteins paxillin and focal adhesion kinase (FAK) mediate a Ca2+-independent length-sensitive signaling pathway in tracheal smooth muscle (30). We used a-toxin-permeabilized tracheal smooth muscle strips to determine whether the length sensitivity of MLC phosphorylation can be regulated by a Ca2+-insensitive signaling pathway and whether the length-sensitivity of active tension depends on the length-sensitivity of myosin activation. Although active tension remained length sensitive, acetylcholine (ACh)-induced MLC phosphorylation was the same at optimal muscle length (Lo) and 0.5 Lo when intracellular Ca2+ was maintained at pCa 7. MLC phosphorylation was also the same at Lo and 0.5 Lo in strips stimulated with 10 µM Ca2+. In contrast, the Ca2+-insensitive tyrosine phosphorylation of FAK and paxillin stimulated by ACh was higher at Lo than at 0.5 Lo. We conclude that the length- sensitivity of MLC phosphorylation depends on length-dependent changes in intracellular Ca2+, but that length-dependent changes in MLC phosphorylation are not the primary mechanism for the length sensitivity of active tension.

Received 1 March 2001; accepted in final form 5 June 2001
APS Manuscript Number A0204-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001