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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.

Abstract：

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 α and β1 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 α subunit of the Maxi-K channel was significantly decreased ~40% while the expression of the β1 subunit was increased ~2-fold at the mRNA level. The increase in β1 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 β1 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.

journal_name

BJU Int

journal_title

BJU international

authors

Aydin M,Wang HZ,Zhang X,Chua R,Downing K,Melman A,DiSanto ME

doi

10.1111/j.1464-410X.2012.11137.x

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

E402-8

issue

8 Pt B

eissn

1464-4096

issn

1464-410X

journal_volume

110

pub_type

杂志文章

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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.