Intercellular Communication and Bladder Function

Christ, George J.; Venkateswarlu, K; Day, Nancy S.; Valcic, Mira; Santizo, Cristian; Zhao, Weixin; Wang, Hong-Zhan; Persson, Katerina; Andersson, Karl‐Erik

doi:10.1007/978-1-4419-8889-8_17

Cited by 5 publications

(7 citation statements)

References 29 publications

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“…28 -32 There was an apparent discordance between the absence of morphologically identifiable junctional structures on the one hand, and electrophysiologic data, which clearly indicated that current injected into one cell flows into neighboring cells. 13,33,34 Consistent with these electrophysiologic observations, recent studies have documented intercellular diffusion of hydrophilic dyes, such as Lucifer yellow, when injected (dialyzed) into detrusor Neurourology and Urodynamics DOI 10.1002/nau myocytes in situ. Furthermore, electron microscopy, immunogold labeling, confocal immunofluorescence, and Western blot techniques have all confirmed the presence of small junctional plaques comprised connexins (Cxs) between human detrusor myocytes.…”

Section: Intercellular Communicationmentioning

confidence: 64%

Detrusor myocyte activity and afferent signaling

Andersson

2009

Neurourology and Urodynamics

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Aims: To discuss (1) mechanisms involved in the generation and control of myocyte contractions and consequent afferent nerve activity and (2) these mechanisms as targets for drugs aimed for treatment of overactive bladder (OAB) symptoms and detrusor overactivity (DO). Methods: Literature review of myocyte activation, bladder afferent nerves, mediators in the bladder, and translational aspects of the findings. Results: During bladder filling, there is normally no parasympathetic outflow from the spinal cord. Despite this, the bladder develops tone during filling and also exhibits non-synchronized local contractions and relaxations that are caused by a basal myogenic mechanical activity that may be reinforced by release of, for example, acetylcholine from non-neuronal and/or neuronal sources or local mediators, such as prostaglandins and endothelins. It is suggested that these spontaneous contractions are able to generate activity in afferent nerves (''afferent noise'') that may contribute to DO and OAB. Conclusions: Spontaneous bladder myocyte contractions and factors that are able to modulate them, as well as the consequent afferent nerve activity, may be targets for drugs meant for treatment of OAB/DO. Neurourol.

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Section: Intercellular Communicationmentioning

confidence: 64%

Detrusor myocyte activity and afferent signaling

Andersson

2009

Neurourology and Urodynamics

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“…One obvious reason for skepticism is related to the apparent absence of the morphological and structural correlates of gap junctions in human (18,21) and rat bladder (28,29). In this regard, a recent report has shown that mRNA for the gap junction protein Cx43 can be detected in the normal rat bladder using RT-PCR techniques (16). Moreover, it is clear that the absence of morphologically detectable gap junctional plaques in rat bladder does not preclude a physiologically relevant contribution of the intercellular pathway to bladder function (9,16,24).…”

Section: Why Does Gene Therapy With Hslo Ameliorate Bladder Overactivmentioning

confidence: 99%

“…In this regard, a recent report has shown that mRNA for the gap junction protein Cx43 can be detected in the normal rat bladder using RT-PCR techniques (16). Moreover, it is clear that the absence of morphologically detectable gap junctional plaques in rat bladder does not preclude a physiologically relevant contribution of the intercellular pathway to bladder function (9,16,24). Finally, as substantially increased Cx43 mRNA levels have recently been reported in the 6-wk obstructed rat bladder (at least 3-to 5-fold; see Ref.…”

Section: Why Does Gene Therapy With Hslo Ameliorate Bladder Overactivmentioning

confidence: 99%

Bladder injection of “naked”hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo

Christ

Day²,

Day³

et al. 2001

American Journal of Physiology-Regulatory, Integrative and Comp

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The goal of these studies was to examine the potential utility of bladder instilled K+ channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 microg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSlo injection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.

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“…However, the functional changes of cell connectivity in DO are not well elucidated, and there is considerable controversy between reports on changes in cell-cell contact in DO after PBOO. Christ et al (7) showed a 75-fold increase of Cx43 mRNA expression compared with the control in DO cells in rats after 6 wk of PBOO, whereas others using scrape loading dye transfer (SLDT) found an increase in dye transfer in the bladder urothelial cells of the rats with acute bladder outflow obstruction. Mori et al (21) revealed an initial increase in Cx43 mRNA expression, but this was followed by a secondary decrease.…”

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confidence: 97%

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

Li¹,

Jiang²,

Hao³

et al. 2007

American Journal of Physiology-Cell Physiology

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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.

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Intercellular Communication and Bladder Function

Cited by 5 publications

References 29 publications

Detrusor myocyte activity and afferent signaling

Detrusor myocyte activity and afferent signaling

Bladder injection of “naked”hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo

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

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