Basolateral localization of native ClC-2 chloride channels in absorptive intestinal epithelial cells and basolateral sorting encoded by a CBS-2 domain di-leucine motif

Peña-Münzenmayer, Gaspar; Catalán, Marcelo A.; Cornejo, Isabel; Figueroa, Carlos D.; Melvin, James E.; Niemeyer, Marı́a Isabel; Cid, L. Pablo; Sepúlveda, Francisco V.

doi:10.1242/jcs.02525

Cited by 87 publications

(92 citation statements)

References 58 publications

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“…In the intestine, ClC-2 is reported to be responsible for Cl Ϫ absorption across the basolateral membrane (28). Because ClC-2 is expressed in airway epithelia (22), we tested whether it was responsible for the basolateral Cl Ϫ current.…”

Section: Regulation Of Basolateral CL ϫ Conductance To Further Undermentioning

confidence: 99%

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Basolateral chloride current in human airway epithelia

Itani¹,

Lamb²,

Melvin³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Electrolyte transport by airway epithelia regulates the quantity and composition of liquid covering the airways. Previous data indicate that airway epithelia can absorb NaCl. At the apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR) provides a pathway for Cl− absorption. However, the pathways for basolateral Cl− exit are not well understood. Earlier studies, predominantly in cell lines, have reported that the basolateral membrane contains a Cl− conductance. However, the properties have varied substantially in different epithelia. To better understand the basolateral Cl− conductance in airway epithelia, we studied primary cultures of well-differentiated human airway epithelia. The basolateral membrane contained a Cl− current that was inhibited by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS). The current-voltage relationship was nearly linear, and the halide selectivity was Cl− > Br− >> I−. Several signaling pathways increased the current, including elevation of cellular levels of cAMP, activation of protein kinase C (PKC), and reduction of pH. In contrast, increasing cell Ca2+ and inducing cell swelling had no effect. The basolateral Cl− current was present in both cystic fibrosis (CF) and non-CF airway epithelia. Likewise, airway epithelia from wild-type mice and mice with disrupted genes for ClC-2 or ClC-3 all showed similar Cl− currents. These data suggest that the basolateral membrane of airway epithelia possesses a Cl− conductance that is not due to CFTR, ClC-2, or ClC-3. Its regulation by cAMP and PKC signaling pathways suggests that coordinated regulation of Cl− conductance in both apical and basolateral membranes may be important in controlling transepithelial Cl− movement.

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Section: Regulation Of Basolateral CL ϫ Conductance To Further Undermentioning

confidence: 99%

“…For example, in portions of the kidney nephron, ClC-Ka/ and ClC-Kb/barttin channels provide pathways for basolateral Cl Ϫ absorption (11). In absorptive intestinal epithelia, ClC-2 is reported to mediate basolateral Cl Ϫ transport (28). In the sweat duct, CFTR accounts for both apical and basolateral Cl Ϫ conductances (33).…”

mentioning

confidence: 99%

Basolateral chloride current in human airway epithelia

Itani¹,

Lamb²,

Melvin³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…68) In colon, ClC-2 is present at the basolateral membranes of surface epithelial cells where it has been proposed to play a rôle in electroneutral salt absorption. [69][70][71] A knockout mouse for ClC-2 presented an unexpected phenotype: animals were blind following a degeneration of photoreceptors and males were infertile as a consequence of the degeneration of germinal cells. 72,73) Several proposed consequences of ClC-2 disruption could not be demonstrated perhaps because the channel function was compensated by other proteins, becoming critical only in the retina and the testis.…”

Section: A Possible Rôle For Clc-2 In Ph O Regulation In Cell Barriersmentioning

confidence: 99%

Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport

Sandoval

Burgos

Sepúlveda

et al. 2011

Biological & Pharmaceutical Bulletin

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The importance of intracellular pH (pH i ) in the regulation of diverse cellular activities ranging from cell proliferation and differentiation to cell cycle, migration and apoptosis has long been recognised. More recently, extracellular pH (pH o ), in particular that of relatively inaccessible compartments or domains that occur between cells in tissues, has begun to be acknowledged as a relevant signal in cell regulation. This should not be surprising given the abundant reports highlighting the pH o -dependence of the activity of membrane proteins facing the extracellular space such as receptors, transporters, ion channels and enzymes. Changes in pH affect the ionisation state of proteins through the effect on their titratable groups. There are proteins, however, which respond to pH shifts with conformational changes that are crucial for catalysis or transport activity. In such cases protons act as signalling molecules capable of eliciting fast and localised responses. We provide examples of ion channels that appear fastidiously designed to respond to extracellular pH in a manner that suggests specific functions in transporting epithelia. We shall also present ideas as to how these channels participate in complex transepithelial transport processes and provide preliminary experiments illustrating a new way to gauge pH o in confined spaces of native epithelial tissue.

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“…Lubiprostone is a prostone that has been extensively shown to treat constipation in well-controlled clinical trials involving thousands of humans (3,4). Lubiprostone received approval from the United States Food and Drug Administration in 2006 under the trade name AMITIZA ® for the long-term treatment of chronic idiopathic constipation in adults (5).…”

Section: To T H E E D I To Rmentioning

confidence: 99%

Erratum

Ueno¹

2009

Critical Reviews in Biochemistry and Molecular Biology

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Basolateral localization of native ClC-2 chloride channels in absorptive intestinal epithelial cells and basolateral sorting encoded by a CBS-2 domain di-leucine motif

Cited by 87 publications

References 58 publications

Basolateral chloride current in human airway epithelia

Basolateral chloride current in human airway epithelia

Extracellular pH in Restricted Domains as a Gating Signal for Ion Channels Involved in Transepithelial Transport

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