Smooth muscle trans-membrane sarcoglycan complex in partial bladder outlet obstruction.
The urinary bladder experiences both distension and contraction as a part of the normal filling and emptying cycle. To empty properly, tension generated intracellularly in a smooth muscle cell must be smoothly and efficiently transferred across its sarcolemma to the basement membrane, which mediates its binding to both the extracellular matrix and to other cells. As a consequence of urethral obstruction, the bladder cannot generate appropriate force to contract the organ, thereby leading to inefficient emptying and associated sequelae. In this study, an animal model of urethral obstruction was utilized to study the membrane-associated structures that transfer tension across the sarcolemma of bladder smooth muscle cells. Immunohistochemical localization of key components of the smooth muscle tension transfer apparatus (TTA) was performed utilizing specific antibodies against:(1) the alpha-chains of type IV collagen, a basement membrane component, and (2) beta-sarcoglycan, an integral membrane protein that is a participant in the physical linkage between the cytoskeleton and the basement membrane. We demonstrate, in obstructed animals, that there is a pronounced disruption of the TTA with a physical displacement of these two components that can be demonstrated at the level of the light microscope using scanning confocal microscopy. Electron microscopy further demonstrates significant increases in the size of the junctional plaques between smooth muscle cells.
Macarak
Edward J
EJ
Department of Anatomy and Cell Biology School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104-6030, USA.
Schulz
Jake
J
Zderic
Stephen A
SA
Sado
Yoshikazu
Y
Ninomiya
Yoshifumi
Y
Polyak
Erzsebet
E
Chacko
Samuel
S
Howard
Pamela S
PS
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001696:Biomechanical Phenomena; D024141:Collagen Type IV / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology*; D011817:Rabbits; D049031:Sarcoglycans / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology*; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000473:pathology*
D024141:Collagen Type IV; D049031:Sarcoglycans