K(2P) TASK-2 and KCNQ1/KCNE3 K(+) channels are major players contributing to intestinal anion and fluid secretion

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Item Type:	Article
Title:	K(2P) TASK-2 and KCNQ1/KCNE3 K(+) channels are major players contributing to intestinal anion and fluid secretion
Creators Name:	Julio-Kalajzić, F., Villanueva, S., Burgos, J., Ojeda, M., Cid, L.P., Jentsch, T.J. and Sepúlveda, F.V.
Abstract:	Anion and fluid secretion across the intestinal epithelium, a process altered in cystic fibrosis and secretory diarrhoea, is mediated by cAMP-activated CFTR Cl(-) channels and requires the simultaneous activity of basolateral K(+) channels to maintain cellular ionic homeostasis and membrane potential. This function is fulfilled by the cAMP-activated K(+) channel formed by the association of pore-forming KCNQ1 with its obligatory KCNE3 {beta}-subunit. Studies using mice show sizable cAMP-activated intestinal anion secretion in the absence of either KCNQ1 or KCNE3 suggesting that an alternative K(+) conductance must compensate for the loss of KCNQ1/KCNE3 activity. We now use double mutant mouse and pharmacological approaches to identify such conductance. Ca(2+) -dependent anion secretion can also be supported by Ca(2+) -dependent K(Ca) 3.1 channels after independent CFTR activation, but cAMP-dependent anion secretion is not further decreased in the combined absence of K(Ca) 3.1 and KCNQ1/KCNE3 K(+) channel activity. We show that K(2P) K(+) channel TASK-2 is expressed in the epithelium of the small and large intestine. Tetrapentylammonium, a TASK-2 inhibitor, abolishes anion secretory current remaining in the absence of KCNQ1/KCNE3 activity. A double mutant mouse lacking both KCNQ1/KCNE3 and TASK-2 showed a much reduced cAMP-mediated anion secretion compared to that observed in the single KCNQ1/KCNE3 deficient mouse. We conclude that KCNQ1/KCNE3 and TASK-2 play major roles in the intestinal anion and fluid secretory phenotype. The persistence of an, admittedly reduced, secretory activity in the absence of these two conductances suggests that further additional K(+) channel(s) as yet unidentified contribute to the robustness of the intestinal anion secretory process.
Keywords:	Epithelial Transport, Fluid Secretion, K(+) Channel Gastrointestinal, Hepatic and Pancreatic Physiology, Animals, Mice
Source:	Journal of Physiology
ISSN:	0022-3751
Publisher:	Wiley
Volume:	596
Number:	3
Page Range:	393-407
Date:	1 February 2018
Official Publication:	https://doi.org/10.1113/JP275178
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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