Increased expression of connexin 43 in the overactive neurogenic detrusor.
OBJECTIVE
The cellular mechanisms involved in unstable uncontrolled detrusor contractions in the human bladder remain unknown. One hypothesis, based on electron microscopical observations and animal studies, is that gap junctions are present in the human detrusor and are increased in patients with detrusor overactivity. Thus intercellular electrical coupling between adjacent detrusor cells would be increased allowing electrical activity to spead more easily within the detrusor muscle mass and more readily generate significant contractions. The aim of this study was to prove this hypothesis.


METHODS
Detrusor biopsies have been obtained from videourodynamically evaluated patients with neurogenic detrusor overactivity (NDO) (n = 19) [group I] and from patients with stress urinary incontinence (SUI) with stable, non-obstructed detrusors (n = 5) [group II] serving as controls. Specimens were fixed, paraffin embedded, sectioned, stained with a monoclonal connexin 43 antibody and evaluated by two blinded examiners using a semiquantitative scale. Connexin 43 mRNA levels were evaluated using quantitative RT-PCR with primers for connexin 43 and for 18S rRNA. The results were correlated with the patients' groups.


RESULTS
Connexin 43 could be identified in cross sections of every detrusor biopsy. In all biopsies from patients with NDO a widespread presence of connexin 43 staining was observed, whereas only a limited presence of connexin 43 staining was observed in the specimen from patients with SUI. Connexin 43 mRNA levels within the detrusor were 3.7 fold higher in the NDO group than in the SUI group (p = 0.017).


CONCLUSIONS
A limited amount of gap junctions seems to be present in every detrusor independently from its urodynamic stability or instability. But there is a significant increase in connexin 43 protein and RNA levels in patients with neurogenic detrusor overactivity underlining their role in intercellular electrical coupling.
Haferkamp
A
A
Department of Urology, University of Bonn, Bonn, Germany. Axel_Haferkamp@med.uni-heidelberg.de
Mundhenk
J
J
Bastian
P J
PJ
Reitz
A
A
Dörsam
J
J
Pannek
J
J
Schumacher
S
S
Schurch
B
B
Büttner
R
R
Müller
S C
SC
D000293:Adolescent; D000328:Adult; D002648:Child; D018031:Connexin 43 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*; D001750:Urinary Bladder, Neurogenic / Q000378:metabolism*
D018031:Connexin 43