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Am J Physiol Renal Physiol 285: F703-F710, 2003. First published June 10, 2003; doi:10.1152/ajprenal.00162.2003
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Partial bladder outlet obstruction alters Ca2+ sensitivity of force, but not of MLC phosphorylation, in bladder smooth muscle

Michaela C. Stanton,1 Michele Clement,2 Edward J. Macarak,3 Stephen A. Zderic,2 and Robert S. Moreland1

1Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia 19102; 2Department of Urology, The Children's Hospital of Philadelphia, Philadelphia 19101; and 3Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania 19101

Submitted 21 May 2003 ; accepted in final form 4 June 2003

Partial bladder outlet obstruction in the rabbit produces changes in bladder function similar to those seen clinically in patients with obstructive uropathies. Whole organ function is significantly altered, as are the smooth muscle cells inside the bladder wall. This study was designed to determine whether outlet obstruction alters smooth muscle function at the level of contractile filaments. Rabbit bladders were partially obstructed for 2 wk. Triton X-100 was used to provide a detergent-skinned bladder smooth muscle preparation that would allow control of the intracellular environment while the ability to shorten and develop force is maintained. Ca2+-force and Ca2+-myosin light chain (MLC) phosphorylation relations and maximal velocity of shortening were determined. The Ca2+ sensitivity of force was significantly lower in tissues from animals subjected to outlet obstruction compared with tissues from control animals. In contrast, no difference was noted in the Ca2+ sensitivity of MLC phosphorylation. Maximal levels of stress and MLC phosphorylation were similar in both animal groups. Maximal velocity of shortening was significantly slower in tissues from outlet-obstructed animals at all Ca2+ concentrations compared with tissues from control animals. Ultrastructurally, detergent skinning had little effect on structural integrity. Moreover, tissues from obstructed animals showed an increase in the number of sarcolemmal attachment plaque structures. We suggest that partial bladder outlet obstruction produces deleterious (e.g., decrease in Ca2+ sensitivity of force) and compensatory (e.g., increase in membrane attachment plaques) changes in bladder smooth muscle cells.

maximal velocity of shortening; Triton X-100 detergent-skinned fibers; attachment plaques; electron micrographs



Address for reprint requests and other correspondence: R. S. Moreland, Dept. of Pharmacology and Physiology, Drexel University College of Medicine, 245 N. 15th St., MS #488, Philadelphia, PA 19102 (E-mail: robert.moreland{at}drexel.edu).




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