Airway epithelial cells—Functional links between CFTR and anoctamin dependent Cl− secretion

Kunzelmann, Karl; Tian, Yuemin; Martins, Joana Raquel; Faria, Diana; Kongsuphol, Patthara; Ousingsawat, Jiraporn; Wolf, Luisa; Schreiber, Rainer

doi:10.1016/j.biocel.2012.06.011

Cited by 38 publications

(36 citation statements)

References 23 publications

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“…Furthermore, the data agree with the premise that CFTR and TMEM16A are functionally linked, as suggested by Kunzelmann et al (17). The simplest explanation of our findings is that the functional linkage is via changes in intracellular Ca 2ϩ .…”

Section: Discussionsupporting

confidence: 93%

Epinephrine stimulation of anion secretion in the Calu-3 serous cell model

Banga

Flaig

Lewis

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Section: Discussionsupporting

confidence: 93%

Epinephrine stimulation of anion secretion in the Calu-3 serous cell model

Banga

Flaig

Lewis

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Studies performed with knockout mice for TMEM16A or TMEM16B [24,25] and knockdown of these channels in specific cell types confirmed their involvement in the generation of CaCCs [12,[26][27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 60%

Multiple effects of anthracene-9-carboxylic acid on the TMEM16B/anoctamin2 calcium-activated chloride channel

Cherian

Menini

Boccaccio

2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Ca(2+)-activated Cl(-) currents (CaCCs) play important roles in many physiological processes. Recent studies have shown that TMEM16A/anoctamin1 and TMEM16B/anoctamin2 constitute CaCCs in several cell types. Here we have investigated for the first time the extracellular effects of the Cl(-) channel blocker anthracene-9-carboxylic acid (A9C) and of its non-charged analogue anthracene-9-methanol (A9M) on TMEM16B expressed in HEK 293T cells, using the whole-cell patch-clamp technique. A9C caused a voltage-dependent block of outward currents and inhibited a larger fraction of the current as depolarization increased, whereas the non-charged A9M produced a small, not voltage dependent block of outward currents. A similar voltage-dependent block by A9C was measured both when TMEM16B was activated by 1.5 and 13μM Ca(2+). However, in the presence of 1.5μM Ca(2+) (but not in 13μM Ca(2+)), A9C also induced a strong potentiation of tail currents measured at -100mV after depolarizing voltages, as well as a prolongation of the deactivation kinetics. On the contrary, A9M did not produce potentiation of tail currents, showing that the negative charge is required for potentiation. Our results provide the first evidence that A9C has multiple effects on TMEM16B and that the negative charge of A9C is necessary both for voltage-dependent block and for potentiation. Future studies are required to identify the molecular mechanisms underlying these complex effects of A9C on TMEM16B. Understanding these mechanisms will contribute to the elucidation of the structure and functional properties of TMEM16B channels.

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“…Thus, intracellular Ca 2+ signals not only stimulate basolateral K + channels and supply additional driving force for apical Cl − secretion but also activate CFTR through inhibition of phosphatases and increase of protein kinase C activity (Fig. 7) [4,25,28,42]. Furthermore, a recent report demonstrates that CFTR and Ano1 are separate but functionally related Cl − channels [36].…”

Section: Discussionmentioning

confidence: 92%

Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine

Schreiber

Faria

Skryabin

et al. 2014

Pflugers Arch - Eur J Physiol

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Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca(2+) and opening of apical Cl(-) channels. In infants and young animals, but not in adults, Ca(2+)-activated chloride channels may cause secretory diarrhea during rotavirus infection. While detailed knowledge exists concerning the contribution of cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) channels, analysis of the role of Ca(2+)-dependent Cl(-) channels became possible through identification of the anoctamin (TMEM16) family of proteins. We demonstrate expression of several anoctamin paralogues in mouse small and large intestines. Using intestinal-specific mouse knockout models for anoctamin 1 (Ano1) and anoctamin 10 (Ano10) and a conventional knockout model for anoctamin 6 (Ano6), we demonstrate the role of anoctamins for Ca(2+)-dependent Cl(-) secretion induced by the muscarinic agonist carbachol (CCH). Ano1 is preferentially expressed in the ileum and large intestine, where it supports Ca(2+)-activated Cl(-) secretion. In contrast, Ano10 is essential for Ca(2+)-dependent Cl(-) secretion in jejunum, where expression of Ano1 was not detected. Although broadly expressed, Ano6 has no role in intestinal cholinergic Cl(-) secretion. Ano1 is located in a basolateral compartment/membrane rather than in the apical membrane, where it supports CCH-induced Ca(2+) increase, while the essential and possibly only apical Cl(-) channel is CFTR. These results define a new role of Ano1 for intestinal Ca(2+)-dependent Cl(-) secretion and demonstrate for the first time a contribution of Ano10 to intestinal transport.

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Airway epithelial cells—Functional links between CFTR and anoctamin dependent Cl− secretion

Cited by 38 publications

References 23 publications

Epinephrine stimulation of anion secretion in the Calu-3 serous cell model

Epinephrine stimulation of anion secretion in the Calu-3 serous cell model

Multiple effects of anthracene-9-carboxylic acid on the TMEM16B/anoctamin2 calcium-activated chloride channel

Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine

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