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Dicer‐deletion in the detrusor reduces contractility and expression of L‐type Ca2+ channels
Author(s) -
Sadegh Mardjaneh Karbalaei,
Ekman Mari,
Rippe Catarina,
Uvelius Bengt,
Swärd Karl,
Albinsson Sebastian
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1140.8
Subject(s) - dicer , gene knockdown , microrna , microbiology and biotechnology , calponin , biology , contractility , endocrinology , rna interference , genetics , gene , actin , rna
MicroRNAs (miRNAs) are small noncoding RNAs which modulate gene expression. Production of most mature miRNAs requires the endonuclease Dicer. Here we investigated the role of miRNAs in the urinary bladder using conditional smooth muscle‐specific Dicer knockout (KO) mice. miR‐145, miR‐22, miR‐125b‐ 5p, miR27a, and miR‐1 were the most highly expressed miRNAs in the detrusor. The knockdown level for these miRNAs ranged between 68 and 99%. Using strip preparations we found that the muscarinic component of the neurogenic contraction was decreased in Dicer‐deficient bladder. A substantially reduced stress in response to high K+ was seen. The expression of L‐type Ca2+ channels (LTCC) was reduced, and only modest reductions of other differentiation markers (desmin, calponin) were noted. Assessment of micturition patterns revealed changes in both frequency and spatial voiding distribution in KO mice. We conclude that the biomechanical consequences of Dicer deletion in the detrusor are dominated by reduced LTCC expression. Deletion of Dicer‐dependent and smooth muscle‐specific miRNAs moreover results in a reduced cholinergic component of neurogenic activation. The effects of Dicer‐deletion on contractility and neuro‐effector transmission act in concert to cause a disturbed micturition pattern in vivo. Supported by Swedish Research Council, Faculty of Medicine at Lund University.