Korean J Urol.  2006 Jul;47(7):722-728. 10.4111/kju.2006.47.7.722.

Altered Expressions of Calcium-Activated Potassium Channel and Connexin in Bladder Mucosae of Stress Urinary Incontinence Patients with Overactive Bladder Symptoms

• Kim DY
• Kim JW
• Yang EK

• KMID: 2294312
• DOI: http://doi.org/10.4111/kju.2006.47.7.722

Abstract

PURPOSE: The aim of this study was to examine how the mRNA and protein levels of calcium activated Kchannel (K(Ca)) and connexin (Cx) change in association with overactive bladder in the bladder mucosae of stress urinary incontinence (SUI) patients.
MATERIALS AND METHODS
Twenty SUI patients were included in our study. Bladder mucosae were obtained, with using cold cup biopsy forceps, from the patients suffering with genuine stress urinary incontinence (group 1, n=7), from the patients suffering with SUI along with urgency and frequency (group 2, n=6), and from the patients suffering with mixed incontinence (group 3, n=7).
RESULTS
The mRNA transcripts of type 2 (SK2) and type 3 (SK3) small conductance K(Ca), Cx26, and Cx43 were highly expressed in the bladder mucosa. The message of large conductance K(Ca)(BK) was significantly decreased in group 3 compared with that in the controls. The SK2 and Cx26 messages in group 3 were also lower than those in groups 1 and 2. In the presence of urge incontinence, the BK and SK2 protein levels were decreased and the Cx26 protein expression was significantly increased in the bladder mucosa of the SUI patients. In contrast, there were no significant differences in the mRNA and protein levels of K(Ca)s and Cxs between groups 1 and group 2.
CONCLUSIONS
Downregulation of both BK and SK2 and upregulation of Cx26 in the bladder mucosa of MI patients may contribute to the alterations of urothelial instability, and this correlate with the symptom severity of bladder instability in SUI patients.

Keyword

Overactive bladder; Urinary stress incontinence; Urothelium; Calcium-activated potassium channel; Connexins

MeSH Terms

Biopsy
Calcium
Connexin 43
Connexins
Down-Regulation
Humans
Mucous Membrane*
Potassium Channels, Calcium-Activated*
RNA, Messenger
Surgical Instruments
Up-Regulation
Urinary Bladder*
Urinary Bladder, Overactive*
Urinary Incontinence*
Urinary Incontinence, Stress
Urinary Incontinence, Urge
Urothelium
Calcium
Connexin 43
Connexins
Potassium Channels, Calcium-Activated
RNA, Messenger

Figure

• 

  Fig. 1 Ethidium bromide-stained gel of the polymerase chain reaction (PCR) products for the calcium activated potassium channel (KCa) subfamilies in human bladder mucosae. BK, IK, and SK denote the large-, intermediate- and small-conductance KCas, respectively.

• 

  Fig. 2 Densitometric analyses of the polymerase chain reaction (PCR) products for BK, SK2 and SK3, corrected for the 18SrRNA value, in each sample. The results are expressed as the fold changes in mRNA (means±SE). BK and SK represent the large- and small-conductance calcium activated potassium channels, respectively. Groups 1, 2 and 3 denote bladder mucosae obtained from the patients suffering with genuine stress urinary incontinence (SUI), SUI with urgency and frequency, and mixed incontinence, respectively. *: p<0.05 vs. the control, †: p<0.05 vs. group 1, ‡: p<0.05 vs. group 2.

• 

  Fig. 3 Expressions of BK, SK2 and SK3 proteins, corrected for β-actin, in each sample. Values are shown in arbitrary units (A.U.) as the mean±SE of human bladder mucosae. BK and SK represent large- and small-conductance calcium activated potassium channels, respectively. Groups 1, 2 and 3 denote bladder mucosae obtained from the patients suffering with genuine stress urinary incontinence (SUI), SUI with urgency and frequency, and mixed incontinence, respectively. *: p<0.05 vs. group 1, †: p<0.05 vs. group 2.

• 

  Fig. 4 Ethidium bromide-stained gel of the polymerase chain reaction (PCR) products for connexin (Cx)26, Cx32, Cx43 and Cx45 in human bladder mucosae.

• 

  Fig. 5 Densitometric analyses of the polymerase chain reaction (PCR) products for connexin (Cx)26, Cx32, Cx43 and Cx45, corrected for the 18SrRNA value, in each sample. The results are expressed as the fold changes in mRNA (means±SE). Groups 1, 2 and 3 denote bladder mucosae obtained from the patients suffering with genuine stress urinary incontinence (SUI), SUI with urgency and frequency, and mixed incontinence, respectively. *: p<0.05 vs. control, †: p<0.05 vs. group 1, ‡: p<0.05 vs. group 2.

• 

  Fig. 6 Expressions of connexin (Cx)26, Cx43, and Cx45 proteins, corrected for β-actin, in each sample. Values are shown in arbitrary units (A.U.) as the mean±SE. Groups 1, 2 and 3 denote bladder mucosae obtained from the patients suffering with genuine stress urinary incontinence (SUI), SUI with urgency and frequency, and mixed incontinence, respectively. *: p<0.05 vs. group 1.

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