PMID- 22520450 OWN - NLM STAT- MEDLINE DCOM- 20121207 LR - 20121001 IS - 1464-410X (Electronic) IS - 1464-4096 (Linking) VI - 110 IP - 8 Pt B DP - 2012 Oct TI - Large-conductance calcium-activated potassium channel activity, as determined by whole-cell patch clamp recording, is decreased in urinary bladder smooth muscle cells from male rats with partial urethral obstruction. PG - E402-8 LID - 10.1111/j.1464-410X.2012.11137.x [doi] AB - OBJECTIVES: To examine the effect of partial urethral obstruction (PUO) on bladder smooth muscle outward potassium current and the contribution of the large-conductance calcium-activated potassium (Maxi-K, BKCa) channel to this activity in smooth muscle cells isolated from bladders of sham-operated and PUO male rats using whole-cell patch clamp recording techniques. To determine the effect of PUO on the expression of the Maxi-K channel alpha and beta1 subunits and in vitro detrusor contractility. MATERIALS AND METHODS: Twenty adult male Sprague-Dawley rats were divided equally into two groups and subjected to surgical ligation of the urethra (PUO) or sham surgery (SHAM). After 2 weeks, the detrusors from PUO and SHAM rats were used for molecular analyses (mRNA and protein quantification of Maxi-K subunits) or organ bath contractility studies, or myocytes were isolated for conventional whole-cell patch clamp analyses. RESULTS: PUO increased bladder mass 2.5-fold and detrusor strips exhibited a more tonic-type contraction and increased contractility compared with controls (SHAM). Iberiotoxin (300 nM) sensitive Maxi-K channel current comprised about 40% of the outward whole-cell current in SHAM bladders but only about 8% in PUO bladders. Expression of the alpha subunit of the Maxi-K channel was significantly decreased ~40% while the expression of the beta1 subunit was increased ~2-fold at the mRNA level. The increase in beta1 expression was confirmed by Western blotting. CONCLUSIONS: Our findings show that obstruction of the rat bladder is associated with decreased Maxi-K channel activity of bladder smooth muscle cells, determined via direct current measurement. Increased expression of the beta1 subunit points to a compensatory reaction to decreased Maxi-K channel activity. Maxi-K channel openers or gene therapy may therefore provide therapeutic benefit for the overactive bladder. CI - (c) 2012 BJU INTERNATIONAL. FAU - Aydin, Memduh AU - Aydin M AD - Department of Urology, Albert Einstein College of Medicine, New York, New York, USA. FAU - Wang, Hong Zhan AU - Wang HZ FAU - Zhang, Xinhua AU - Zhang X FAU - Chua, Rowena AU - Chua R FAU - Downing, Keith AU - Downing K FAU - Melman, Arnold AU - Melman A FAU - DiSanto, Michael E AU - DiSanto ME LA - eng GR - R01 DK077116/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120423 PL - England TA - BJU Int JT - BJU international JID - 100886721 RN - 0 (Large-Conductance Calcium-Activated Potassium Channels) SB - IM MH - Animals MH - Cells, Cultured MH - Large-Conductance Calcium-Activated Potassium Channels/*physiology MH - Male MH - Myocytes, Smooth Muscle/*physiology MH - Patch-Clamp Techniques MH - Rats MH - Rats, Sprague-Dawley MH - Urethral Obstruction/*physiopathology MH - Urinary Bladder/*physiopathology EDAT- 2012/04/24 06:00 MHDA- 2012/12/12 06:00 CRDT- 2012/04/24 06:00 PHST- 2012/04/24 06:00 [entrez] PHST- 2012/04/24 06:00 [pubmed] PHST- 2012/12/12 06:00 [medline] AID - 10.1111/j.1464-410X.2012.11137.x [doi] PST - ppublish SO - BJU Int. 2012 Oct;110(8 Pt B):E402-8. doi: 10.1111/j.1464-410X.2012.11137.x. Epub 2012 Apr 23.