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Decreased expression of TRAAK channels in Hirschsprung’s disease: a possible cause of postoperative dysmotility

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Abstract

Aim of the study

Potassium (K+) channels with a two-pore domain (K2P) are a large family of hyperpolarising ion channels which play a key role in cell excitability. This family comprises three members: TREK-1, TREK-2 and TRAAK. TRAAK channels have previously been reported to be expressed in murine enteric ganglia. To date, no data exist regarding TRAAK channel expression in the human colon. Thus, we designed this study to investigate TRAAK gene 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 TRAAK gene expression, and immunolabelling of TRAAK proteins was visualized using confocal microscopy.

Main results

Confocal microscopy revealed TRAAK protein expression within both neurons and interstitial cells of Cajal in the myenteric plexus, with a reduction in both ganglionic HSCR colon and aganglionic HSCR colon, compared to controls. qRT-PCR analysis revealed a significant downregulation of the TRAAK gene in both aganglionic and ganglionic HSCR specimens compared to controls (p < 0.05).

Conclusions

TRAAK gene expression is significantly downregulated in HSCR colon, suggesting a role for these ion channels in colonic neurotransmission. TRAAK downregulation within ganglionic specimens highlights the dysfunctional nature of ganglia in this region.

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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, Bina Parekh & Prem Puri

Authors
  1. Anne-Marie O’Donnell
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  2. Hiroki Nakamura
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  3. Bina Parekh
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  4. Prem Puri
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Correspondence to Prem Puri.

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O’Donnell, AM., Nakamura, H., Parekh, B. et al. Decreased expression of TRAAK channels in Hirschsprung’s disease: a possible cause of postoperative dysmotility. Pediatr Surg Int 35, 1431–1435 (2019). https://doi.org/10.1007/s00383-019-04572-4

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  • DOI: https://doi.org/10.1007/s00383-019-04572-4

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