Ouabain-sensitive H,K-ATPase Functions as Na,K-ATPase in Apical Membranes of Rat Distal Colon

Rajendran, Vazhaikkurichi M.; Sangan, Pitchai; Geibel, John P.; Binder, Henry J.

doi:10.1074/jbc.275.17.13035

Cited by 34 publications

(17 citation statements)

References 35 publications

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“…As shown in Fig. 3, the presence of Na + /K + -ATPase a 1 subunit in the apical membranes can be excluded, allowing us to conclude that the previously measured Na + -and K + -stimulated ATPase activity found in the apical membranes of the colon is not due to Na + / K + -ATPase, but could be associated with some form(s) of the colonic H + /K + -ATPase, as suggested previously [27,28].…”

Section: Discussionsupporting

confidence: 72%

Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon

Scheiner‐Bobis¹,

Hübschle

Diener

2002

European Journal of Biochemistry

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Palytoxin stimulated a cation-dependent short-circuit current (Isc) in rat distal and proximal colon in a concentration-dependent fashion when applied to the mucosal surface of the tissue. The distal colon exhibited a higher sensitivity to the toxin. The palytoxin-induced Isc was blocked by vanadate but was resistant to ouabain or scilliroside, suggesting the conversion of a vanadate-sensitive H + /K + -ATPase into an electrogenic cation transporter. Cation substitution experiments with basolaterally depolarized tissues suggested an apparent permeability of the palytoxin-induced conductance of Na + >K + >Li + . Immunohistochemical control experiments confirmed the absence of the Na + /K + -ATPase in the apical membrane. Consequently, the pore-forming action of palytoxin is not restricted to Na + /K + -ATPase but is also observed with the colonic H + /K + -ATPase.Keywords: ATPase; colon; palytoxin; Isc; ion channel. P 2C -type ATPases are oligomeric enzymes consisting of a and b subunits [1]. The sodium pump from the plasma membranes of animal cells, a member of this group, generates a sodium gradient by pumping three Na + ions out of the cell and two K + ions into the cell for each ATP hydrolyzed [2]. This sodium gradient is the driving force of all secondarily active transporters and a presupposition for neuronal conduction of signals.The closest relatives of the sodium pump are the proton pumps from gastric and colon epithelial cells [3]. Although these pumps are not identical, they both catalyze an active secretion of protons driven by ATP hydrolysis. Unlike the sodium pump, however, both proton pumps are electroneutral: each transports one K + ion from the luminal side into the cytosol for each H + secreted.Several naturally occurring toxins have been identified as specific inhibitors of the sodium pump. Among them, the so-called cardioactive steroids or cardiac glycosides are not only known for their ability to selectively target the sodium pump but are widely used as effective medication for patients with heart failure or heart insufficiency [4]. Palytoxin, a toxin isolated from corals of the family Palythoa (e.g. Palythoa caribaeorum), is also a highly specific inhibitor of the sodium pump [5,6]. This most potent toxin (for rodents the LD 50 is 10-250 ng per kg of body weight) of animal origin can also be found together with ciguatoxin, maitotoxin, or gambierol in fishes that contribute to ciguatera poisonings [7,8]. Palytoxin is a rather unique and large molecule with the structural formula C 129 H 223 N 3 O 54 . The molecule can be divided into three subdomains, each connected by peptide bonds: a large N-terminal polyhydroxy x-amino acid followed by a dehydro-b-alanine residue and an aminopropanol group. The number of free hydroxyl groups is 42 [9,10]. Unlike the cardioactive steroids, however, which inhibit both ATP hydrolysis and ion conduction, palytoxin acts by arresting the ionophore of the pump into a permanently open state. Thus, in this case, inhibition of ATP hydrolysis is no longer associated ...

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Section: Discussionsupporting

confidence: 72%

Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon

Scheiner‐Bobis¹,

Hübschle

Diener

2002

European Journal of Biochemistry

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“…Given ouabain was used as a specific blocker for Na + -K + -ATPase in these studies, and the location of Na + -K + -ATPase has not been verified immunocytochemically, we should keep in mind that ouabain-inhibitable H + -K + -ATPase α subunit may co-exist [35,36]. H + -K + -ATPase has been found in re-absorptive epithelial tissues, including kidney and gastrointestinal tract [36,37].…”

Section: I-2 Na + -K + -Atpase and Ca 2+ -Atpasementioning

confidence: 99%

“…H + -K + -ATPase has been found in re-absorptive epithelial tissues, including kidney and gastrointestinal tract [36,37]. It has been reported H + -K + -ATPase can form a hybrid with Na + -K + -ATPase [36].…”

Section: I-2 Na + -K + -Atpase and Ca 2+ -Atpasementioning

confidence: 99%

Electrolyte and Fluid Transport in Mesothelial Cells

Ji¹,

Nie²

2008

JEBP

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Mesothelial cells are specialized epithelial cells, which line the pleural, pericardial, and peritoneal cavities. Accumulating evidence suggests that the monolayer of mesothelial cells is permeable to electrolyte and fluid, and thereby govern both fluid secretion and re-absorption in the serosal cavities. Disorders in these salt and fluid transport systems may be fundamental in the pathogenesis of pleural effusion, pericardial effusion, and ascites. In this review, we discuss the location, physiological function, and regulation of active transport (Na + -K + -ATPase) systems, cation and anion channels (Na + , K + , Cl − , and Ca 2+ channels), antiport (exchangers) systems, and symport (co-transporters) systems, and water channels (aquaporins). These secretive and absorptive pathways across mesothelial monolayer cells for electrolytes and fluid may provide pivotal therapeutical targets for novel clinical intervention in edematous diseases of serous cavities. Keywords mesothelioma; ion channel; permeability; effusion; filtration; ENaC Mesothelial cells are specialized epithelial cells that line the serous cavities, including the pleural, pericardial, and peritoneal cavities in addition to internal organs [1]. While the mesothelium was first described more than a century ago, one of its critical essential functions, namely, its active roles in transerosal transport, in particular, cavity fluid secretion and reabsorption, was long overlooked. Only in last two decades compelling evidence accumulated that mesothelial cells actively transport electrolytes and fluid and, in turn, regulate liquid volume within the cavities. The mesothelium, on the basis of recent increasing experimental evidence, both in vitro and in vivo, is less permeable to electrolytes than was previously assumed, with ion permeability characteristics similar to those in epithelia [2,3]. Herein this article we will review the expression and biophysical features of salt and fluid transport systems, both active and passive, that have been identified in mesothelial cells (Fig. 1, Tables 1 and 2). I. ION CHANNELS AND ATPASE I-1. Amiloride-Inhibitable Cation ChannelsThe epithelial sodium channel (ENaC), as a major pathway which participates in sodium movement across the apical membrane of polarized epithelial cells, has been cloned and characterized [4][5][6] ENaC subunits have been cloned to date, namely α-, β-, γ-, δ-, and ε-ENaC [7]. The biophysical properties of various ENaC channels depend on their subunit compositions. When expressed in oocytes one of "conductive" subunits (α, δ, and ε-ENaC) can form a channel sharing identical biophysical properties to three-subunit channels composed of both a "conductive" subunit and two "non-conductive" subunits, namely, β-and γ-ENaCs. When α-, β-, and γ-ENaC subunits are assembled together, the result is a 4-to 6-pS channel that is highly selective for Na + over K + . In contrast, two-subunit α β-and α γ-ENaC channels display diverse amiloride sensitivity, conductance, and Na + permeability [8]. ENaC is...

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“…5). Active K ϩ absorption is restricted to the mammalian distal colon of rat, rabbit, and guinea pig (153,314,460 (488). Potassium that has been taken up from the luminal side is released to the blood side by basolateral K ϩ channels and probably by the electroneutral KCl cotransporter KCC1 (520).…”

mentioning

confidence: 99%

Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease

Kunzelmann

Mall

2002

Physiological Reviews

588

571

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The colonic epithelium has both absorptive and secretory functions. The transport is characterized by a net absorption of NaCl, short-chain fatty acids (SCFA), and water, allowing extrusion of a feces with very little water and salt content. In addition, the epithelium does secret mucus, bicarbonate, and KCl. Polarized distribution of transport proteins in both luminal and basolateral membranes enables efficient salt transport in both directions, probably even within an individual cell. Meanwhile, most of the participating transport proteins have been identified, and their function has been studied in detail. Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na+ channels (ENaC), the Na+-K+-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK. Acute regulation of absorption may occur by a Na+ feedback mechanism and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl− secretion in the adult colon relies on luminal CFTR, which is a cAMP-regulated Cl− channel and a regulator of other transport proteins. As a consequence, mutations in CFTR result in both impaired Cl− secretion and enhanced Na+ absorption in the colon of cystic fibrosis (CF) patients. Ca2+- and cAMP-activated basolateral K+ channels support both secretion and absorption of electrolytes and work in concert with additional regulatory proteins, which determine their functional and pharmacological profile. Knowledge of the mechanisms of electrolyte transport in the colon enables the development of new strategies for the treatment of CF and secretory diarrhea. It will also lead to a better understanding of the pathophysiological events during inflammatory bowel disease and development of colonic carcinoma.

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Ouabain-sensitive H,K-ATPase Functions as Na,K-ATPase in Apical Membranes of Rat Distal Colon

Cited by 34 publications

References 35 publications

Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon

Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon

Electrolyte and Fluid Transport in Mesothelial Cells

Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease

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Ouabain-sensitive H,K-ATPase Functions as Na,K-ATPase in Apical Membranes of Rat Distal Colon

Cited by 34 publications

References 35 publications

Action of palytoxin on apical H+/K+‐ATPase in rat colon

Action of palytoxin on apical H+/K+‐ATPase in rat colon

Electrolyte and Fluid Transport in Mesothelial Cells

Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease

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Product

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Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon

Action of palytoxin on apical H⁺/K⁺‐ATPase in rat colon