TREK-1 channel expression in smooth muscle as a target for regulating murine intestinal contractility: Therapeutic implications for motility disorders

Ruolin Ma, Mohsen Seifi, Maria Papanikolaou, James F. Brown, Jerome D. Swinny, Anthony Lewis

Research output: Contribution to journalArticle

Abstract

© 2018 Ma, Seifi, Papanikolaou, Brown, Swinny and Lewis. Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+) channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR), immunohistochemistry and confocal microscopy. The contribution of mechano-gated K2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate) induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.
Original languageEnglish
JournalFrontiers in Physiology
Volume9
Issue numberMAR
DOIs
Publication statusPublished - 6 Mar 2018

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Ileum
Smooth Muscle
Colon
Baths
Gastrointestinal Tract
Immunohistochemistry
Flufenamic Acid
Riluzole
Therapeutics
Muscle Tonus
Gastrointestinal Motility
Irritable Bowel Syndrome
Potassium Channels
Confocal Microscopy
potassium channel protein TREK-1
Pathology
Phenotype
Neurons
Polymerase Chain Reaction
Genes

Cite this

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title = "TREK-1 channel expression in smooth muscle as a target for regulating murine intestinal contractility: Therapeutic implications for motility disorders",
abstract = "{\circledC} 2018 Ma, Seifi, Papanikolaou, Brown, Swinny and Lewis. Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+) channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR), immunohistochemistry and confocal microscopy. The contribution of mechano-gated K2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate) induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.",
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TREK-1 channel expression in smooth muscle as a target for regulating murine intestinal contractility: Therapeutic implications for motility disorders. / Ma, Ruolin; Seifi, Mohsen; Papanikolaou, Maria; Brown, James F.; Swinny, Jerome D.; Lewis, Anthony.

In: Frontiers in Physiology, Vol. 9, No. MAR, 06.03.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - TREK-1 channel expression in smooth muscle as a target for regulating murine intestinal contractility: Therapeutic implications for motility disorders

AU - Ma, Ruolin

AU - Seifi, Mohsen

AU - Papanikolaou, Maria

AU - Brown, James F.

AU - Swinny, Jerome D.

AU - Lewis, Anthony

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AB - © 2018 Ma, Seifi, Papanikolaou, Brown, Swinny and Lewis. Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractility is disrupted. Potassium (K+) channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K2P channels in mouse ileum and colon. Expression and distribution of the K2P channel family were investigated using quantitative RT-PCR (qPCR), immunohistochemistry and confocal microscopy. The contribution of mechano-gated K2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate) induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.

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DO - 10.3389/fphys.2018.00157

M3 - Article

VL - 9

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - MAR

ER -