Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase

Nakamura, Nobuhiro; Suzuki, Yoshiro; Sakuta, Hidenari; Ookata, Kayoko; Kawahara, Katsumasa; Hirose, Shigehisa

doi:10.1042/bj3420329

Cited by 105 publications

(73 citation statements)

References 24 publications

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“…Hence, these signals could be derived from other cell types of the mucosa. In addition, the studies did not compare expression levels of other members of the K channel family on either genomic or proteomic levels, and hence a variety of conflicting data have been published (7,10,16,18).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, some groups used RT-PCR or Northern blot analysis to compare RNA levels of some but not all members of the K channel family (7,10,16,18). None of these studies was done on purified PCs.…”

Section: Discussionmentioning

confidence: 99%

“…Because the primary purpose of this work was to attempt to identify the K channel associated with acid secretion, we compared the level of K channel gene expression in the fundic epithelium and the 80 and Ͼ99% pure PC suspensions. Table 3 shows the results of the analysis of 23 of the 82 K channel subunits present on the microarray, 4 of which were previously suggested to be present in PCs (7,10,16,18).…”

Section: Purification Of Gastric Pcs To Homogeneitymentioning

confidence: 99%

“…Four different members of the K channel family have been proposed as the principle K channel at this site (7,10,16,18), largely based on immunohistochemical localization studies in the gastric mucosa. The present study combines a novel method of parietal cell purification to homogeneity followed by comparative (subtractive) oligonucleotide expression microarray analysis to find proteins that could represent the apical K secretory channel.…”

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confidence: 99%

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Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion

Lambrecht

Yakubov

Scott

et al. 2005

Physiological Genomics

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Genomic microarray analysis of genes specifically expressed in a pure cell isolate from a heterocellular organ identified the likely K efflux channel associated with the gastric H-K-ATPase. The function of this channel is to supply K to the luminal surface of the pump to allow H for K exchange. KCNQ1-KCNE2 was the most highly expressed and significantly enriched member of the large variety of K channels expressed in the gastric epithelium. The function of this K channel in acid secretion was then shown by inhibition of secretion in isolated gastric glands with specific KCNQ inhibitors and by colocalization of the channel with the H-K-ATPase in the secretory canaliculus of the parietal cell. KCNQ1-KCNE2 appears to be the K efflux channel that is essential for gastric acid secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Purification Of Gastric Pcs To Homogeneitymentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion

Lambrecht

Yakubov

Scott

et al. 2005

Physiological Genomics

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“…There has been considerable controversy as to the nature of the K and Cl efflux pathways and the K entry pathway. [17][18][19][20][21] The comparative transcriptome of the parietal cell afforded significant clues in that there were only some channels selectively enriched as compared with the gastric epithelium. The K channels found were the basolateral inward rectifying Kir5.1/Kir4.2 channel responsible for K repletion of K lost during secretion, the voltage insensitive but pH sensitive KCNQ1/KCNE2 K channel 19,22 and the CLIC6 Cl channel 23 as K and Cl secreting channels across the canalicular membrane.…”

Section: Potassium and Chloride Conductancesmentioning

confidence: 99%

The Gastric H,K ATPase as a Drug Target

Sachs¹,

Shin²,

Vagin³

et al. 2007

Journal of Clinical Gastroenterology

139

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The recent progress in therapy if acid disease has relied heavily on the performance of drugs targeted against the H,K ATPase of the stomach and the H2 receptor antagonists. It has become apparent in the last decade that the proton pump is the target that has the likelihood of being the most sustainable area of therapeutic application in the regulation of acid suppression. The process of activation of acid secretion requires a change in location of the ATPase from cytoplasmic tubules into the microvilli of the secretory canaliculus of the parietal cell. Stimulation of the resting parietal cell, with involvement of F-actin and ezrin does not use significant numbers of SNARE proteins, because their message is depleted in the pure parietal cell transcriptome. The cell morphology and gene expression suggest a tubule fusion-eversion event. As the active H,K ATPase requires efflux of KCl for activity we have, using the transcriptome derived from 99% pure parietal cells and immunocytochemistry, provided evidence that the KCl pathway is mediated by a KCQ1/KCNE2 complex for supplying K + and CLIC6 for supplying the accompanying Cl − . The pump has been modeled on the basis of the structures of different conformations of the sr Ca ATPase related to the catalytic cycle. These models use the effects of site directed mutations and identification of the binding domain of the K competitive acid pump antagonists or the defined site of binding for the covalent class of proton pump inhibitors. The pump undergoes conformational changes associated with phosphorylation to allow the ion binding site to change exposure from cytoplasmic to luminal exposure. We have been able to postulate that the very low gastric pH is achieved by lysine 791 motion extruding the hydronium ion bound to carboxylates in the middle of the membrane domain. These models also allow description of the K + entry to form the K + liganded form of the enzyme and the reformation of the ion site inward conformation thus relating the catalytic cycle of the pump to conformational models. The mechanism of action of the proton pump inhibitor class of drug is discussed along with the cysteines covalently bound with these inhibitors. The review concludes with a discussion of the mechanism of action and binding regions of a possible new class of drug for acid control, the K + competitive acid pump antagonists.Keywords the H; K ATPase; acid secretion; acid pump antagonist; proton pump inhibitor Acid secretion by the human stomach results in a median diurnal pH of 1.4. At the turn of the 19th century, it was recognized that acid secretion is involved in peptic ulcer disease Reprints: Dr George Sachs, DSc, MD, Membrane Biology, Bldg 113, Rm 324, 11301 Wilshire Blvd., Los Angeles, CA 90073 (gsachs@ucla.edu). Until the introduction of cimetidine, a histamine-2 receptor blocker, 3 there was no therapy that was effective in suppressing acid secretion acceptable to patients. The introduction of this medication and other histamine-2 receptor antagonists revolutionized the t...

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Mechanisms of CSF secretion by the choroid plexus

Speake

Whitwell

Kajita

et al. 2000

Microsc. Res. Tech.

161

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The epithelial cells of the choroid plexus secrete cerebrospinal fluid (CSF), by a process that involves the movement of Na+, Cl− and HCO3− from the blood to the ventricles of the brain. This creates the osmotic gradient, which drives the secretion of H2O. The unidirectional movement of the ions is achieved due to the polarity of the epithelium, i.e., the ion transport proteins in the blood‐facing (basolateral) are different to those in the ventricular (apical) membranes. Saito and Wright (1983) proposed a model for secretion by the amphibian choroid plexus, in which secretion was dependent on activity of HCO3− channels in the apical membrane. The patch clamp method has now been used to study the ion channels expressed in rat choroid plexus. Two potassium channels have been observed that have a role in maintaining the membrane potential of the epithelial cell, and in regulating the transport of K+ across the epithelium. An inward‐rectifying anion channel has also been identified, which is closely related to ClC‐2 channels, and has a significant HCO3− permeability. This channel is expressed in the apical membrane of the epithelium where it may play an important role in CSF secretion. A model of CSF secretion by the mammalian choroid plexus is proposed that accommodates these channels and other data on the expression of transport proteins in the choroid plexus. Microsc. Res. Tech. 52:49–59, 2001. © 2001 Wiley‐Liss, Inc.

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Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase

Cited by 105 publications

References 24 publications

Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion

Identification of the K efflux channel coupled to the gastric H-K-ATPase during acid secretion

The Gastric H,K ATPase as a Drug Target

Mechanisms of CSF secretion by the choroid plexus

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