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Impaired contractility and detrusor hypertrophy in cavin-1-deficient mice

Publiceringsår: 2012
Språk: Engelska
Sidor: 179-185
Publikation/Tidskrift/Serie: European Journal of Pharmacology
Volym: 689
Nummer: 1-3
Dokumenttyp: Artikel
Förlag: Elsevier

Sammanfattning

Caveolae are membrane invaginations present in a variety of cell types. Formation of caveolae depends on caveolins and on the more recently discovered family of proteins known as the cavins. Genetic ablation of caveolin-1 was previously shown to give rise to a number of urogenital alterations, but the effects of cavin-1 deletion on urogenital function remain unknown. Here we characterised detrusor contractility and structure in cavin-1-deficient mice. Electron microscopy demonstrated essentially complete lack of caveolae in the knock-out detrusor, and immunoblotting disclosed reduced levels of cavin-3 and of all caveolin proteins. Bladder weight was increased in male knock-out mice, and length-tension relationships demonstrated a reduction in depolarisation-induced contraction. Contractility in response to muscarinic receptor activation was similarly reduced. Despite these functional changes, micturition patterns were similar in conscious and freely moving animals and diuresis was unchanged. Our breeding additionally disclosed that the number of knock-out mice generated in heterozygous crosses was lower than expected, suggesting embryonic/perinatal lethality. In conclusion, this is the first study to show that cavin-1 is critical for detrusor caveolae and for the overall contractility and structure of the urinary bladder. (C) 2012 Elsevier B.V. All rights reserved.

Disputation

Nyckelord

  • Medicine and Health Sciences
  • PTRF (Polymerase 1 and transcript release factor)
  • SDPR (Serum
  • deprivation protein response)
  • SRBC (sdr-related gene product that binds
  • to c kinase)
  • Pacsin2
  • Caveolae
  • Carbachol
  • Purinergic

Övriga

Published
Yes
  • ISSN: 0014-2999

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