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Changes in dense-body structures in airway smooth muscle adapted to different lengths

University of British Columbia

Dense bodies in smooth muscle are thought to be the equivalents of Z-disks found in striated muscle. Using three-dimensional reconstruction of serial sections of electron micrographs of ASM, we have confirmed previous studies showing that dense-body (DB) aggregates inside smooth muscle cells resemble “stringy” structures lying in parallel with the myosin filaments. We found that the cable-like structure consists of DBs closely strung together by actin and intermediate filaments. This finding questions the conventional belief that DBs play the role of the Z-disks. In this study we examined further the structural changes in the DB “cable” in ovine tracheal smooth muscle adapted to different lengths (length adaptation); specifically we examined the length ratio between the DB cable length (in three-dimensional space) and the segment length of the muscle cell in which the cable was embedded. This length ratio, or normalized DB-cable length, gave us a measurement of the “slackness” of the DB cables in the cell. Length adaptation was a process in which ASM regained its force generating capacity after a change in the length of the muscle cell. The process involved brief (10 see) electrical field stimulations once every 5 mm applied to the muscle held isometrically. With a 50% muscle shortening, the average normalized DB-cable length increased by 10%, the cables then straightened out slightly but significantly during length adaptation to the shortened length, decreasing the length by 3% from the 10% increase. With a 50% stretch, the average normalized DB-cable length decreased by -15% and 27% in the length adapted and non-adapted states, respectively. The most significant finding of this study is that passive tension in ASM cells is negatively correlated to the normalized DB-cable length (DB-cable/cell-segment length ratio). That is, higher passive tension is associated tauter DB cables. This suggests that the DB cables may be important in maintaining passive tension in smooth muscle cells. Understanding how DB cables adapt to length changes and how their structural integrity is modulated intracellularly is important for a better understanding of the roles ASM plays in the stiffening of airways and pathophysiology of asthma.

Text

2010-10-29

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/29646

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/