Biomechanical properties and innervation of the female caveolin-1-deficient detrusor |
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Authors: | Sadegh Mardjaneh Karbalaei Ekman Mari Rippe Catarina Sundler Frank Wierup Nils Mori Michiko Uvelius Bengt Swärd Karl |
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Institution: | Department of Experimental Medical Science, Lund University, Biomedical Centre, Lund, Sweden. |
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Abstract: | BACKGROUND AND PURPOSECaveolin-1-deficiency is associated with substantial urogenital alterations. Here, a mechanical, histological and biochemical characterization of female detrusors from wild-type and caveolin-1-deficient (KO) mice was made to increase the understanding of detrusor changes caused by lack of caveolae.EXPERIMENTAL APPROACHLength–tension relationships were generated, and we recorded responses to electrical field stimulation, the muscarinic receptor agonist carbachol and the purinoceptor agonist ATP. Tyrosine nitration and the contents of caveolin-1, cavin-1, muscarinic M3 receptors, phospholipase Cβ1, muscle-specific kinase (MuSK) and L-type Ca2+ channels were determined by immunoblotting. Innervation was assessed by immunohistochemistry.KEY RESULTSBladder to body weight ratio was not changed, nor was there any change in the optimum circumference for force development. Depolarization- and ATP-induced stress was reduced, as was carbachol-induced stress between 0.1 and 3 µM, but the supramaximal relative (% K+) response to carbachol was increased, as was M3 expression. The scopolamine-sensitive component of the electrical field stimulation response was impaired, and yet bladder nerves contained little caveolin-1. The density of cholinergic nerves was unchanged, whereas CART- and CGRP-positive nerves were reduced. Immunoblotting revealed loss of MuSK.CONCLUSIONS AND IMPLICATIONSAblation of caveolae in the female detrusor leads to generalized impairment of contractility, ruling out prostate hypertrophy as a contributing factor. Cholinergic neuroeffector transmission is impaired without conspicuous changes in the density of cholinergic nerves or morphology of their terminals, but correlating with reduced expression of MuSK. |
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Keywords: | caveolae carbachol ATP purine receptor CGRP CART NPK synaptophysin caveolin cavin lower urinary tract dysfunction MuSK |
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