Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo

Christ, George J.; Day, Nancy S.; Day, M.; Zhao, Weixin; Persson, Katarina; Pandita, Raj K.; Andersson, Karl‐Erik

doi:10.1152/ajpregu.00030.2002

Cited by 101 publications

(118 citation statements)

References 35 publications

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“…Cx43 is a biogenetic precursor of gap junctions, which are the main connexons expressed in astrocytes (11)(12)(13). It has been reported that Cx43 hemichannels are sensitive to various stimuli, including osmotic stimulation (19). A connexin hemichannel spans unopposed plasma membrane regions and, following docking with partners, produces a gap junction channel that allows for direct intercellular communication.…”

Section: Discussionmentioning

confidence: 99%

Involvement of connexin43 in the acute hyperosmotic stimulus-induced synthesis and release of vasopressin in the supraoptic nucleus of rats

Jiang

Wang

et al. 2014

Molecular Medicine Reports

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Abstract. There is evidence that astroglial connexin43 (Cx43) in the supraoptic nucleus (SON) is required for the hyperosmolarity-induced increase in Fos protein expression in magnocellular neurosecretory cells (MNCs). In the present study, the role of astroglial Cx43 in the synthesis and release of vasopressin (VP) by MNCs in the SON subjected to hyperosmotic stimulus was examined. The results revealed that the VP levels in the SON and plasma were increased following acute hyperosmotic stimulus. Treatment of MNCs with Cx43-specific antisense oligodeoxynucleotides (ASODN), which temporarily reduced Cx43 protein production, limited the VP synthesis and release induced by a hyperosmotic stimulus. Similarly, the addition of gap junction and Cx43 hemichannel blockers also attenuated the VP synthesis and release induced by an acute hyperosmotic stimulus. A high extracellular [Ca 2+ ]( [Ca 2+ ] o ) has been demonstrated to reduce the gap junction activity or opening probability of Cx54 hemichannels. Notably, it was identified that high [Ca 2+ ] o attenuated the VP synthesis and release induced by acute hyperosmotic stimulus, while low [Ca 2+ ] o had a weak or no effect. These results suggested that Cx43 participates in the VP synthesis and release induced by hyperosmotic stimulation in the SON.

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Section: Discussionmentioning

confidence: 99%

Involvement of connexin43 in the acute hyperosmotic stimulus-induced synthesis and release of vasopressin in the supraoptic nucleus of rats

Jiang

Wang

et al. 2014

Molecular Medicine Reports

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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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“…Astrocytes release glutamate through various mechanisms, for example, P2X7 receptor [6] , exocytosis [7,8] , and Cx43 hemichannels [9] . Cx43 is a main connexin protein expressed in astrocytes [10][11][12] and is sensitive to various stimuli including osmotic stimulation [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Hypertonic stimulation induces synthesis and release of glutamate in cultured rat hypothalamic astrocytes and C6 cells

et al. 2008

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Objective To investigate whether hypertonic saline (HS) can induce the synthesis and release of glutamate in cultured hypothalamic astrocytes or C6 cell line. Methods Astrocytes were isolated, cultured, purified and identified from the hypothalamus of newborn rat (1 day). The astrocytes were randomly divided into five groups: isotonic (IS) and HS groups, astrocytes were incubated by IS and HS (320 mOsm NaCl) medium, respectively, for 1, 3, 5, 10 or 15 min; carbenoxolone (CBX) +IS and CBX+HS groups, astrocytes were pre-treated with CBX (100 mmol/L) for 1 h at 37 ºC in a 5% CO2 / 95% atmosphere, then removed to IS and HS medium, respectively, for 1, 3, 5, 10 or 15 min; Ca 2+ +HS group, astrocytes were pre-incubated with Ca 2+ (1 000 μmol/L) for 1 h at 37 ºC in a 5% CO 2 / 95% atmosphere, followed by a wash with isotonic FBS/DMEM, and then removed to hypertonic saline for 1, 3, 5, 10 or 15 min. The media of five groups were collected to analyze the medium glutamate concentration with high performance liquid chromatography. The astrocytes were fixed and double immunofluorescent stained with anti-glial fibrillary acidic protein (GFAP) and anti-glutamate. The C6 cells were divided into four groups: IS, HS, CBX+IS and CBX+HS groups, and used for quantitative measurement of glutamate in cells by flow cytometry (FCM). Results (1) Anti-GFAP immunofluorescent signal revealed no significant difference among various time points in each group, or among the five groups. (2) The anti-glutamate immunofluorescent signal was increased in HS group and peaked at 5 min, and decreased and returned to the level of IS group at 15 min (P < 0.01 vs the 5 min of HS group). In CBX+HS group, the glutamate intensity was higher than that in CBX+IS and HS groups. (3) The medium glutamate concentration had no change after treatment with HS for 1 and 3 min, while increased markedly after treatment for 5 min to 15 min (P < 0.01 vs 1 min and 3 min). On the contrary, the medium glutamate concentrations in the CBX+HS or Ca 2+ +HS group were significant lower than that in the HS group (P < 0.01). (4) FCM showed HS and CBX+HS induced glutamate increase in C6 cells. Conclusion HS induced cultured rat hypothalamic astrocytes or C6 cells to synthesize and release glutamate; CBX could block glutamate release, but could not disrupt glutamate synthesis.

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Increased connexin43-mediated intercellular communication in a rat model of bladder overactivity in vivo

Cited by 101 publications

References 35 publications

Involvement of connexin43 in the acute hyperosmotic stimulus-induced synthesis and release of vasopressin in the supraoptic nucleus of rats

Involvement of connexin43 in the acute hyperosmotic stimulus-induced synthesis and release of vasopressin in the supraoptic nucleus of rats

Neural Control of the Lower Urinary Tract

Hypertonic stimulation induces synthesis and release of glutamate in cultured rat hypothalamic astrocytes and C6 cells

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