Activation of the basolateral membrane Cl−conductance essential for electrogenic K+secretion suppresses electrogenic Cl−secretion

He, Qin; Halm, Susan T.; Zhang, Jin; Halm, Dan R.

doi:10.1113/expphysiol.2010.055038

Cited by 31 publications

(26 citation statements)

References 54 publications

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“…At any rate, expression and localization in apical or basolateral membranes of Ano1 appear to be age dependent, with more apical expression in the colon of mice aging 14 days and younger, while expression is shifted to the basolateral membrane in older animals, which have also been examined in the present study [27,38]. Basolateral expression of Ano1 has also been found in adult guinea pig colon [16]. We demonstrated earlier that Ca 2+ -mediated Cl − secretion is absent in the colon of Ano1−/− pups [37].…”

Section: Discussionmentioning

confidence: 51%

“…Electrolyte secretion is controlled by a number of hormones leading to increase in either intracellular cAMP or Ca 2+ , with consecutive activation of cystic fibrosis transmembrane conductance regulator (CFTR) and Ca 2+ -activated Cl − channels (CaCC), respectively [14,24]. While the contribution of CFTR to intestinal Cl − secretion is well defined, controversial results have been reported for CaCC, which has been identified recently as anoctamin 1 (TMEM16A; Ano1) and which was detected in the basolateral rather than in the apical membrane of adult intestinal epithelial cells [6,16,22,38,44,55]. The role of Ano1 for intestinal Cl − secretion, and also whether Ano1 is the only relevant anoctamin in the intestine, is therefore unclear.…”

Section: Introductionmentioning

confidence: 98%

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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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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 98%

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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“…␤-Adrenergic activation of electrogenic K ϩ secretion conforms to the cellular model for Cl Ϫ secretion with the inclusion of apical membrane K ϩ channels (21,29). Sensitivity to IbTx and paxilline supported a reliance on K Ca 1.1 for ϳ50% of apical membrane K ϩ exit (Fig.…”

Section: Discussionmentioning

confidence: 90%

“…A variety of secretagogues stimulate colonic K ϩ secretion apparently via cells capable of Cl Ϫ secretion (29,64) with an output ranging from primarily K ϩ secretion (Figs. 1 and 3) to mostly Cl Ϫ secretion (Fig.…”

Section: Discussionmentioning

confidence: 99%

Role of the BK channel (K_Ca1.1) during activation of electrogenic K⁺ secretion in guinea pig distal colon

Zhang

Halm

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Secretagogues acting at a variety of receptor types activate electrogenic K(+) secretion in guinea pig distal colon, often accompanied by Cl(-) secretion. Distinct blockers of K(Ca)1.1 (BK, Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (I(sc)) associated with K(+) secretion. Mucosal addition of IbTx inhibited epinephrine-activated I(sc) ((epi)I(sc)) and transepithelial conductance ((epi)G(t)) consistent with K(+) secretion occurring via apical membrane K(Ca)1.1. The concentration dependence of IbTx inhibition of (epi)I(sc) yielded an IC(50) of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibited (epi)G(t) with an IC(50) of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibited (epi)I(sc) and (epi)G(t) by ∼50%. IbTx and paxilline also inhibited I(sc) activated by mucosal ATP, supporting apical K(Ca)1.1 as a requirement for this K(+) secretagogue. Responses to IbTx and paxilline indicated that a component of K(+) secretion occurred during activation of Cl(-) secretion by prostaglandin-E(2) and cholinergic stimulation. Analysis of K(Ca)1.1α mRNA expression in distal colonic epithelial cells indicated the presence of the ZERO splice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits K(Ca)β1 and K(Ca)β4 also was demonstrated. Immunolocalization supported the presence of K(Ca)1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K(+) secretion involving apical membrane K(Ca)1.1 during activation by several secretagogue types, but the observed K(+) secretion likely required the activity of additional K(+) channel types in the apical membrane.

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“…4b, c). Similarly expression of Ano 1 was found in the basolateral membrane of colonic epithelial cells of adult guinea pigs where it may contribute to production of electrogenic K + secretion [39]. In contrast, clear luminal staining is seen in the distal colon of younger animals (Fig.…”

Section: Developmental Aspects Of Anoctaminsmentioning

confidence: 93%

Anoctamins

Kunzelmann

Tian

Martins

et al. 2011

Pflugers Arch - Eur J Physiol

104

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Endogenous Ca(2+)-activated Cl(-) channels (CaCC) demonstrate biophysical and pharmacological properties that are well represented in cells overexpressing anoctamin 1 (Ano 1, TMEM16A), a protein that has been identified recently as CaCC. Proteins of the anoctamin family (anoctamin 1-10, TMEM16A-K) are widely expressed. The number of reports demonstrating their physiological and clinical relevance is quickly rising. Anoctamins gain additional interest through their potential role in cell volume regulation and malignancy. Available data suggest that Ano 1 forms stable dimers and probably liaise with accessory proteins such as calmodulin or other anoctamins. In order to understand how anoctamins produce Ca(2+)-activated Cl(-) currents, it will be necessary to obtain better insight into their molecular structure, interactions with partner proteins, and mode of activation.

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Activation of the basolateral membrane Cl⁻conductance essential for electrogenic K⁺secretion suppresses electrogenic Cl⁻secretion

Abstract: Adrenaline activates transient Cl

Cited by 31 publications

References 54 publications

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

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

Role of the BK channel (K_Ca1.1) during activation of electrogenic K⁺ secretion in guinea pig distal colon

Anoctamins

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Activation of the basolateral membrane Cl−conductance essential for electrogenic K+secretion suppresses electrogenic Cl−secretion

Abstract: Adrenaline activates transient Cl

Cited by 31 publications

References 54 publications

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

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

Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon

Anoctamins

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Activation of the basolateral membrane Cl⁻conductance essential for electrogenic K⁺secretion suppresses electrogenic Cl⁻secretion

Role of the BK channel (K_Ca1.1) during activation of electrogenic K⁺ secretion in guinea pig distal colon