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Altered expression of KCNG3 and KCNG4 in Hirschsprung’s disease

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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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References

  1. Heinemann S, Rettig J, Scott V, Parcej DN, Lorra C, Dolly J, Pongs O (1994) The inactivation behaviour of voltage-gated K-channels may be determined by association of alpha- and beta-subunits. J Physiol Paris 88(3):173–180

    Article  CAS  PubMed  Google Scholar 

  2. Regnier G, Bocksteins E, Marei WF, Pintelon I, Timmermans JP, Leroy J, Snyders DJ (2017) Targeted deletion of the Kv6.4 subunit causes male sterility due to disturbed spermiogenesis. Reprod Fertil Dev 29(8):1567–1575. https://doi.org/10.1071/RD16075

    Article  CAS  PubMed  Google Scholar 

  3. Bocksteins E, Snyders DJ, Holmgren M (2017) Independent movement of the voltage sensors in KV2.1/KV6.4 heterotetramers. Sci Rep 7:41646. https://doi.org/10.1038/srep41646

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Lee MY, Ha SE, Park C, Park PJ, Fuchs R, Wei L, Jorgensen BG, Redelman D, Ward SM, Sanders KM, Ro S (2017) Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures. PLoS One 12(4):e0176031. https://doi.org/10.1371/journal.pone.0176031

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Ha SE, Lee MY, Kurahashi M, Wei L, Jorgensen BG, Park C, Park PJ, Redelman D, Sasse KC, Becker LS, Sanders KM, Ro S (2017) Transcriptome analysis of PDGFRalpha + cells identifies T-type Ca2 + channel CACNA1G as a new pathological marker for PDGFRalpha + cell hyperplasia. PLoS One 12(8):e0182265. https://doi.org/10.1371/journal.pone.0182265

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Curro D (2014) K(+) channels as potential targets for the treatment of gastrointestinal motor disorders. Eur J Pharmacol 733:97–101. https://doi.org/10.1016/j.ejphar.2014.03.049

    Article  CAS  PubMed  Google Scholar 

  7. Ward SM, Sanders KM (2006) Involvement of intramuscular interstitial cells of Cajal in neuroeffector transmission in the gastrointestinal tract. J Physiol 576(Pt 3):675–678

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Rolle U, Piotrowska AP, Nemeth L, Puri P (2002) Altered distribution of interstitial cells of Cajal in Hirschsprung disease. Arch Pathol Lab Med 126 (8):928–933. https://doi.org/10.1043/0003-9985(2002)126%3C0928:ADOICO%3E2.0.CO;2

    Article  PubMed  Google Scholar 

  9. Piotrowska A, Solari V, Puri P (2003) Distribution of interstitial cells of Cajal in the internal anal sphincter of patients with internal anal sphincter achalasia and Hirschsprung’s disease. Arch Pathol Lab Med 127(9):1192–1195

    PubMed  Google Scholar 

  10. Nemeth L, Puri P (2001) Three-dimensional morphology of c-Kit-positive cellular network and nitrergic innervation in the human gut. Arch Pathol Lab Med 125(7):899–904

    CAS  PubMed  Google Scholar 

  11. Kurahashi M, Nakano Y, Hennig GW, Ward SM, Sanders KM (2012) Platelet-derived growth factor receptor alpha-positive cells in the tunica muscularis of human colon. J Cell Mol Med 16(7):1397–1404. https://doi.org/10.1111/j.1582-4934.2011.01510.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. O’Donnell A, Coyle D, Puri P (2016) Deficiency of platelet-derived growth factor receptor-α-positive cells in Hirschsprung’s disease colon. World J Gastroenterol 22(12):3335–3340

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, Dublin 12, Ireland

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

Authors
  1. Anne Marie O’Donnell
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  2. Hiroki Nakamura
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  3. Christian Tomuschat
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  4. Naoum Fares Marayati
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  5. Prem Puri
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Correspondence to Prem Puri.

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O’Donnell, A.M., Nakamura, H., Tomuschat, C. et al. Altered expression of KCNG3 and KCNG4 in Hirschsprung’s disease. Pediatr Surg Int 35, 193–197 (2019). https://doi.org/10.1007/s00383-018-4394-2

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  • DOI: https://doi.org/10.1007/s00383-018-4394-2

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