Changes of gap junctional cell-cell communication in overactive detrusor in rats

Abstract

To evaluate the changes in intercellular communication through gap junctions in detrusor overactivity (DO), we studied 23 adult female Wistar rats with DO after partial outflow obstruction (DO group) and 13 sham-operated rats (control group). The two groups were compared by means of urodynamics, light and electron microscopy, expression of Cx40, Cx43, and Cx45 mRNA genes with RT-PCR, Cx43 protein with Western blot analysis, and functional intercellular communication with scrape loading dye transfer (SLDT) and fluorescence recovery after photobleaching (FRAP). The number of gap junctions and the expression of connexin mRNA and Cx43 protein were increased in DO rats, and intercellular communication through gap junctions increased after 6 wk of partial outflow obstruction as assessed with SLDT and FRAP techniques. The findings provide a theoretical rationale for using Cx43 antagonists and gap junction inhibitors in the treatment of patients with overactive detrusor secondary to partial bladder outflow obstruction.

Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle

“…In the normal bladder, connexin 43 is mainly located in interstitial cells around muscle bundles (34). However, in overactive bladders under obstruction, connexin 43 is upregulated in the detrusor smooth muscle, as reported by Christ and colleagues and other groups (5,11,23,25), strongly suggesting a correlation between them. In contrast, connexin 45 is reported to locate predominantly between smooth muscle cells (18,34), but the expression level remains unchanged in obstructed bladders (18,34).…”

“…The fluorescent emission was analyzed before bleaching, immediately after bleaching, and 4 min after bleaching by Fluoview image-analysis software 5.0 (Olympus). The recovery rates were measured using the method described elsewhere (23). Briefly, the fluorescence intensity before bleaching and immediately after bleaching was set as 100 and 0%, respectively.…”

“…However, the precise mechanism of overactivity in the obstructed bladder has not yet been elucidated. Bladder overactivity in BOO is believed to result from neurogenic changes in detrusor innervation or myogenic changes in detrusor excitability (3,23,41). Recent investigations of the mechanisms of neurogenic changes have suggested nerve growth factor, neurotransmitters, and c-fiber activity as candidate mediators of the process (6,41,42).…”

“…It has been suggested that gap junctions play an important role in the coupling of bladder smooth muscle cells (BSMC). Gap junctions consist of channels in the cell surface that connect neighboring cells by allowing the movement of molecules smaller than 1,000 Da, thereby sustaining and transferring chemical and electrical excitation between cells (10,23). Connexins are the principal structural components of gap junctions (22).…”

Construction and functional analysis of luciferase reporter plasmid containing connexin43 gene promoter

“…Gap junctions consist of channels between neighboring cells, mediating transfer of chemical molecules or electrical stimulation [14][15]. In some vascular smooth muscle diseases, Cx43 up-regulation and coupling of smooth muscle occurred, thereby inducing change in contractile property through upregulation of cell-cell communication [16][17][18].…”