Increased Expression of Connexin 43 in the Overactive Neurogenic Detrusor

Haferkamp, Axel; Mundhenk, Jens; Bastian, Patrick J.; Reitz, André; Dörsam, J.; Pannek, Jürgen; Schumacher, Stefan; Schurch, Brigitte; Büttner, Reinhard; Müller, Stefan

doi:10.1016/j.eururo.2004.08.020

Cited by 64 publications

(47 citation statements)

References 18 publications

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Section: Intercellular Communicationmentioning

confidence: 91%

“…Cx45 37 and Cx43 40,41 appear to be the most prominent Cxs expressed in human detrusor smooth muscle tissue and cultured cells. 39 Observations in tissue biopsies from patients with neurogenic DO 40 and urgency symptoms 41 clearly demonstrated an increase in the presence of Cx43-derived gap junction channels in detrusor muscle. These clinical data are consistent with experimental observations in a rodent model of partial urethral outlet obstruction, 42 which documented a dramatic increase of Cx43 mRNA levels associated with bladder hypertrophy and overactivity following 6 weeks of obstruction.…”

Section: Intercellular Communicationmentioning

confidence: 91%

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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: 91%

Section: Intercellular Communicationmentioning

confidence: 91%

Detrusor myocyte activity and afferent signaling

Andersson

2009

Neurourology and Urodynamics

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“…Increased detrusor myogenic activity which is an important contributor to BOO induced DO can be induced by many mechanisms including: denervation supersensitivity of cholinergic (muscarinic) receptors (583), increases in purinergic receptor mediated contractile responses as well as expression of purinergic receptors such as P2X1 (75,485), changes in the cell-to-cell communication in detrusor muscles due to upregulation of gapjunction proteins such as connexin 43 (112,253) and increased in the number of interstitial cells (328, 349).…”

Section: Bladder Outlet Obstructionmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

2009

Encyclopedia of Neuroscience

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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“…Connexin43 is one of the gap junction proteins, and it is the best-characterized connexin in rat and human bladder smooth muscle cells (5,9,14). Expression of Connexin43 increases after BOO in rats and is also increased in patients with detrusor overactivity (5,9,10). It has been reported that 18alpha-glycyrrhetinic acid acts as a blocker of gap junction communication (3).…”

mentioning

confidence: 99%

“…Partial BOO is an established experimental model for producing detrusor overactivity in animals, which causes signifi cant changes of bladder smooth muscle contraction (17). It has been reported that an increased intercellular communication via gap junctions in the bladder may play an important role in the onset of detrusor overactivity in both rats and humans (5,10). Therefore, it is possible that administration of a gap junction blocker may be useful for the treatment of detrusor overactivity.…”

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confidence: 99%

A gap junction blocker inhibits isolated whole bladder activity in normal rats and rats with partial bladder outlet obstruction

et al. 2006

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We examined the effect of 18alpha-glycyrrhetinic acid (18alpha-GA), a gap junction blocker, or propiverine hydrochloride on the activity of isolated whole bladders obtained from intact rats and rats with partial bladder outlet obstruction (BOO). Thirty-two female Sprague-Dawley rats were divided into an intact group and a BOO group. The whole bladder was harvested from each rat and isovolumetric cystometry was performed in Krebs solution. Changes of bladder activity were recorded after addition of 18alpha-GA or propiverine hydrochloride to the perfusate. Propiverine hydrochloride inhibited the amplitude and duration of contraction in both intact and BOO groups. Propiverine hydrochloride also reduced the baseline bladder pressure in the BOO group, but not in the intact group. In contrast, 18alpha-GA inhibited the amplitude and duration of bladder contraction, and also reduced the baseline pressure, in both intact and BOO groups. BOO bladders showed inhibition of the amplitude and duration of bladder contraction at lower concentrations of 18alpha-GA than intact bladders. A gap junction blocker suppressed the in vitro activity of BOO bladders more effectively than that of intact bladders. Therefore, inhibition of intercellular communication in the bladder via gap junctions may be useful for treating detrusor overactivity, as well as propiverine hydrochloride.

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Increased Expression of Connexin 43 in the Overactive Neurogenic Detrusor

Cited by 64 publications

References 18 publications

Detrusor myocyte activity and afferent signaling

Detrusor myocyte activity and afferent signaling

Neural Control of the Lower Urinary Tract

A gap junction blocker inhibits isolated whole bladder activity in normal rats and rats with partial bladder outlet obstruction

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