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Pediatric Surgery International

Published in:

01-02-2019 | Original Article

Altered expression of KCNG3 and KCNG4 in Hirschsprung’s disease

Authors: Anne Marie O’Donnell, Hiroki Nakamura, Christian Tomuschat, Naoum Fares Marayati, Prem Puri

Published in: Pediatric Surgery International | Issue 2/2019

Abstract

Purpose

Voltage-gated potassium ion channels have long been implicated in gastrointestinal motility. Recent studies have highlighted the role of voltage-gated channel subfamily G member 3 (KCNG3) and 4 (KCNG4) genes in the electrical functioning of interstitial cells of Cajal and PDGFRα⁺ cells of the mouse colon. We designed this study to investigate KCNG3 and KCNG4 expression in the normal human colon and in Hirschsprung’s disease (HSCR).

Methods

HSCR tissue specimens (n = 6) were collected at the time of pull-through surgery, while control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 6). qRT-PCR analysis was undertaken to quantify KCNG3 and KCNG4 gene expression, and immunolabelling of KCNG3 and KCNG4 proteins was visualized using confocal microscopy.

Results

qRT-PCR analysis revealed significant downregulation of the KCNG3 and KCNG4 genes in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed KCNG3 and KCNG4 expression within neurons, ICC and PDGFRα⁺ cells of the myenteric plexus and smooth muscle layers, with a reduction in both proteins in aganglionic and ganglionic HSCR colon compared to controls.

Conclusion

KCNG3 and KCNG4 gene expression is significantly downregulated in HSCR colon, suggesting a role for these genes in colonic motility. KCNG3 and KCNG4 downregulation within ganglionic specimens highlights the physiologically abnormal nature of this segment in HSCR patients.

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Title: Altered expression of KCNG3 and KCNG4 in Hirschsprung’s disease
Authors: Anne Marie O’Donnell
Hiroki Nakamura
Christian Tomuschat
Naoum Fares Marayati
Prem Puri
Publication date: 01-02-2019
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 2/2019
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-018-4394-2

At a glance: The STEP trials

Springer Medicine

Altered expression of KCNG3 and KCNG4 in Hirschsprung’s disease

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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