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.
BJU Int
; 110(8 Pt B): E402-8, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22520450
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 ß1 subunits and in vitro detrusor contractility. MATERIALS ANDMETHODS:
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 ß1 subunit was increased ~2-fold at the mRNA level. The increase in ß1 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 ß1 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Obstrução Uretral
/
Bexiga Urinária
/
Miócitos de Músculo Liso
/
Canais de Potássio Ativados por Cálcio de Condutância Alta
Limite:
Animals
Idioma:
En
Revista:
BJU Int
Assunto da revista:
UROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos