Evidence that two distinct crypt cell types secrete chloride and potassium in human colon

Linley, John E.; Loganathan, Arun; Kopanati, S; Sandle, Geoffrey I.; Hunter, Malcolm

doi:10.1136/gutjnl-2013-304695

Cited by 25 publications

(26 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meprin-β, a metalloendopeptidase involved in the detachment and release of mucus from goblet cells, as well as in the modulation of mucus properties (57), was poorly expressed in HF-fed mice compared with SD-fed mice. Therefore, a combination of down-regulation of Meprin-β expression reducing the apical release of mucin vesicles and dysfunction of the CFTR/NKCC1 complex altering the balance of electrolytes in the luminal fluid (62), all associated with an impairment of the PPAR-γ pathway (59), are likely to account for the collapse of the mucus barrier (55,57). Moreover, when we treated the mice with rosiglitazone, the Meprin-β staining was stronger in HF-rosi mice compared with HF-fed mice.…”

Section: Discussionmentioning

confidence: 99%

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

Tomas

Mulet

Saffarian

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

203

146

View full text Add to dashboard Cite

Diet is among the most important factors contributing to intestinal homeostasis, and basic functions performed by the small intestine need to be tightly preserved to maintain health. Little is known about the direct impact of high-fat (HF) diet on small-intestinal mucosal defenses and spatial distribution of the microbiota during the early phase of its administration. We observed that only 30 d after HF diet initiation, the intervillous zone of the ileum—which is usually described as free of bacteria—became occupied by a dense microbiota. In addition to affecting its spatial distribution, HF diet also drastically affected microbiota composition with a profile characterized by the expansion of Firmicutes (appearance of Erysipelotrichi), Proteobacteria (Desulfovibrionales) and Verrucomicrobia, and decrease of Bacteroidetes (family S24-7) and Candidatus arthromitus. A decrease in antimicrobial peptide expression was predominantly observed in the ileum where bacterial density appeared highest. In addition, HF diet increased intestinal permeability and decreased cystic fibrosis transmembrane conductance regulator (Cftr) and the Na-K-2Cl cotransporter 1 (Nkcc1) gene and protein expressions, leading to a decrease in ileal secretion of chloride, likely responsible for massive alteration in mucus phenotype. This complex phenotype triggered by HF diet at the interface between the microbiota and the mucosal surface was reversed when the diet was switched back to standard composition or when mice were treated for 1 wk with rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ). Moreover, weaker expression of antimicrobial peptide-encoding genes and intervillous bacterial colonization were observed in Ppar-γ–deficient mice, highlighting the major role of lipids in modulation of mucosal immune defenses.

show abstract

Section: Discussionmentioning

confidence: 99%

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

Tomas

Mulet

Saffarian

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

203

146

View full text Add to dashboard Cite

show abstract

“…In human colonic mucosa, apical BK channels are also responsible for K ϩ secretion [which is induced by cAMP (117)] but are located exclusively in goblet cells (88). An earlier study had reported an expression only in surface cells and cells in the upper 20% of the crypt axis and had found that they are mainly composed of ␤ 1 and ␤ 3 subunits (116).…”

Section: K ϩ Channelsmentioning

confidence: 99%

“…They are the dominant basolateral K ϩ channels in human colonocytes (but not in goblet cells) and are expressed throughout the length of crypt axis (2,88). In fact, they are required for the cAMP-stimulated Cl Ϫ secretion through CFTR (cystic fibrosis transmembrane conductance regulator), which is independent of BK channel activation (117).…”

Section: K ϩ Channelsmentioning

confidence: 99%

Role of epithelial ion transports in inflammatory bowel disease

Magalhães

Cabral

Soares‐da‐Silva

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na+-K+-ATPase (NKA), Na+/H+ exchangers (NHEs), epithelial Na+ channels (ENaC), and K+ channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.

show abstract

“…BK channels | LRRC26 | secretory epithelium | salivary glands | SLO1 L arge-conductance, voltage-and Ca 2+ -regulated BK-type channels are widely expressed proteins, found not only in excitable cells, such as neurons, muscle, and endocrine cells, but also nonexcitable cells, including salivary (1) and lacrimal gland (2) acinar cells, and colonic crypt cells (3). Given the almost ubiquitous expression of BK channels among cells that play quite distinct physiological roles, it is particularly important to define the specific properties of BK channels in a given cell type and determine what the specific physiological role played by BK channels in a given cell may be.…”

mentioning

confidence: 99%

Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells

Yang

González-Pérez

Mukaibo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca 2+ -and voltage-dependent BK-type K + channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca 2+ , suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KO mice with a β-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons. We establish the presence of LRRC26 protein in eight secretory tissues or tissues with significant secretory epithelium and show that LRRC26 protein coassembles with the pore-forming BK α-subunit in at least three tissues: lacrimal gland, parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar cells, LRRC26 KO shifts BK gating to be like α-subunit-only BK channels. Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K + ] in saliva. LRRC26-containing BK channels are competent to contribute to resting K + efflux at normal cell membrane potentials with resting cytosolic Ca 2+ concentrations and likely play a critical physiological role in supporting normal secretory function in all secretory epithelial cells.L arge-conductance, voltage-and Ca 2+ -regulated BK-type channels are widely expressed proteins, found not only in excitable cells, such as neurons, muscle, and endocrine cells, but also nonexcitable cells, including salivary (1) and lacrimal gland (2) acinar cells, and colonic crypt cells (3). Given the almost ubiquitous expression of BK channels among cells that play quite distinct physiological roles, it is particularly important to define the specific properties of BK channels in a given cell type and determine what the specific physiological role played by BK channels in a given cell may be. A hallmark of BK channels is their dual regulation by both membrane voltage and cytosolic Ca 2+ (4), both properties embedded within the tetramer of pore-forming α-subunits of each BK channel (5). However, the specific range of voltages over which a BK channel is active at a given Ca 2+ concentration is markedly dependent on the identity of regulatory subunits that can coassemble with the α-subunit in the mature channel complex. Of the two families of known BK regulatory subunits, β (6-11) and γ (12-14), an important feature of many of these subunits is the ability to shift the range of activation voltages at a given Ca 2+ . Although there is growing information about the loci of expression and functional roles of BK channels containing specific β-subunits (15), much less is known about those BK channels containing the γ1 (LRRC26, leucine-rich-repeat-containing subunit 26) subunit. However, LRRC26 is particularly fascinating because it causes the largest shift in BK gating (approximately −120 mV) of any known non-pore-forming regulatory subunit, resulting in BK channels that...

show abstract

Evidence that two distinct crypt cell types secrete chloride and potassium in human colon

Cited by 25 publications

References 56 publications

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

Role of epithelial ion transports in inflammatory bowel disease

Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK channels in secretory epithelial cells

Contact Info

Product

Resources

About