title: Biomechanical properties and innervation of the female caveolin-1-deficient detrusor.
abstract: OBJECTIVE
  Caveolin-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.
  
  
  METHODS
  Length-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 C(β1), muscle-specific kinase (MuSK) and L-type Ca(2+) channels were determined by immunoblotting. Innervation was assessed by immunohistochemistry.
  
  
  RESULTS
  Bladder 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
  Ablation 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.
authors.affiliation: Department of Experimental Medical Science, Lund University, Biomedical Centre, Lund, Sweden.
authors.forename: Mardjaneh Karbalaei
authors.initials: MK
authors.lastname: Sadegh
authors.forename: Mari
authors.initials: M
authors.lastname: Ekman
authors.forename: Catarina
authors.initials: C
authors.lastname: Rippe
authors.forename: Frank
authors.initials: F
authors.lastname: Sundler
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
authors.forename: Michiko
authors.initials: M
authors.lastname: Mori
authors.forename: Bengt
authors.initials: B
authors.lastname: Uvelius
authors.forename: Karl
authors.initials: K
authors.lastname: Swärd
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001696:Biomechanical Phenomena; D002217:Carbachol / Q000494:pharmacology; D021941:Caveolae / Q000473:pathology / Q000502:physiology; D051242:Caveolin 1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004231:Diuresis; D004558:Electric Stimulation; D005260:Female; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size; D011470:Prostatic Hyperplasia / Q000150:complications; D009435:Synaptic Transmission; D001743:Urinary Bladder / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D017931:DNA Primers; D000255:Adenosine Triphosphate; D002217:Carbachol