Potassium secretion is inhibited by metabolic acidosis in rabbit cortical collecting ducts in vitro

Tabei, Keiko; Muto, Shigeaki; Furuya, H; Sakairi, Y.; Ando, Yumiko; Asano, Yoshihide

doi:10.1152/ajprenal.1995.268.3.f490

Cited by 10 publications

(10 citation statements)

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“…Like the physiologic base-line potassium channels expressed in pancreatic acinar cells, TWIK-2 is inhibited by intracellular acidity but is not sensitive to a number of potassium channel inhibitors, including tetraethylammonium, Ba 2ϩ , and 4-aminopyridine (20). In addition, barium-insensitive potassium currents have been described in the kidney (22)(23)(24). Weak inward rectifiers have also been reported in hepatocytes (25) as well as in eosinophils (26).…”

Section: Twik-2 Potassium Channelmentioning

confidence: 99%

TWIK-2, a New Weak Inward Rectifying Member of the Tandem Pore Domain Potassium Channel Family

Chavez

Gray

Zhao

et al. 1999

Journal of Biological Chemistry

128

101

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Potassium channels are found in all mammalian cell types, and they perform many distinct functions in both excitable and non-excitable cells. These functions are subserved by several different families of potassium channels distinguishable by primary sequence features as well as by physiological characteristics. Of these families, the tandem pore domain potassium channels are a new and distinct class, primarily distinguished by the presence of two pore-forming domains within a single polypeptide chain. We have cloned a new member of this family, TWIK-2, from a human brain cDNA library. Primary sequence analysis of TWIK-2 shows that it is most closely related to TWIK-1, especially in the pore-forming domains. Northern blot analysis reveals the expression of TWIK-2 in all human tissues assayed except skeletal muscle. Human TWIK-2 expressed heterologously in Xenopus oocytes is a non-inactivating weak inward rectifier with channel properties similar to TWIK-1. Pharmacologically, TWIK-2 channels are distinct from TWIK-1 channels in their response to quinidine, quinine, and barium. TWIK-2 is inhibited by intracellular, but not extracellular, acidification. This new clone reveals the existence of a subfamily in the tandem pore domain potassium channel family with weak inward rectification properties.

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Section: Twik-2 Potassium Channelmentioning

confidence: 99%

TWIK-2, a New Weak Inward Rectifying Member of the Tandem Pore Domain Potassium Channel Family

Chavez

Gray

Zhao

et al. 1999

Journal of Biological Chemistry

128

101

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“…One well recognised factor is pH, which has been shown to influence amiloride-sensitive sodium absorption in various epithelia [15,16,18,22,25,27,44]. A reduction in cytosolic pH (pH i ) reduces the Na + permeability of the mucosal membrane of frog skin [18,44], toad bladder [26], and principal cells in rabbit CCD [41]. Indeed, the pH-mediated regulation of ENaC is thought to play a role in epithelial "crosstalk", to co-ordinate sodium entry and exit via the apical and basolateral membranes [18].…”

Section: Introductionmentioning

confidence: 99%

Conservation of pH sensitivity in the epithelial sodium channel (ENaC) with Liddle's syndrome mutation

Konstas

Mavrelos

Korbmacher

2000

Pfl�gers Archiv European Journal of Physiology

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Gain-of-function mutations of the epithelial Na+ channel (ENaC) cause a rare form of hereditary hypertension, Liddle's syndrome. How these mutations lead to increased channel activity is not yet fully understood. Since wild-type ENaC (wt-ENaC) is highly pH-sensitive, we wondered whether an altered pH-sensitivity of ENaC might contribute to the hyperactivity of ENaC with Liddle's syndrome mutation (Liddle-ENaC). Using Xenopus laevis oocytes as an expression system, we compared the pH-sensitivity of wt-ENaC (alphabetagammarENaC) and Liddle-ENaC (alphabeta(R564stop)gammarENaC). Oocytes were assayed for an amiloride-sensitive (2 microM) inward current (deltaIami) at -60 mV holding potential and cytosolic pH was altered by changing the extracellular pH in the presence of 60 mM sodium acetate. Alternatively, cytosolic acidification was achieved by proton loading the cells using a proton-coupled oligopeptide transporter (PepT-1) co-expressed in the oocytes together with ENaC. Cytosolic but not extracellular acidification substantially reduced deltaIami while cytosolic alkalinisation had a stimulatory effect. This pH-sensitivity was largely preserved in oocytes expressing Liddle-ENaC. The inhibition of wt-ENaC and Liddle-ENaC by cytosolic acidification was independent of so-called sodium-feedback inhibition, since it was not associated with a concomitant increase in intracellular Na+ concentration estimated from the reversal potential of deltaIami. In addition C-terminal deletions in the alpha or gamma subunits or in all three subunits of ENaC did not abolish the inhibitory effect of cytosolic acidification. We conclude that ENaC's pH-sensitivity is not mediated by its cytoplasmic C-termini and that an altered pH-sensitivity of ENaC does not contribute to the pathophysiology of Liddle's syndrome.

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“…1 In a previous study we demonstrated the effect of basolateral acidosis on potassium transport in rabbit CCD. 5 Basolateral acidosis suppressed potassium secretion and depolarized the transepithelial voltage through independent conductances of sodium and bicarbonate. In the course of these experiments, we observed that when HEPES buffer solution was used for the elimination of bicarbonate instead of standard KRB solution, V T was hyperpolarized, although the pH of both solutions had been adjusted to a constant 7.4.…”

Section: Discussionmentioning

confidence: 99%

“…5,10 The potassium concentration was measured with a microanalysis flame photometer (AFA-707-D; Apel, Saitama, Japan). Net potassium flux (J K ) was calculated using the equation: 5…”

Section: Net Potassium Fluxmentioning

confidence: 99%

“…4 We have previously demonstrated that basolateral acidosis depolarized transepithelial voltage and reduced net potassium secretion in the rabbit CCD. 5 However, the role of alkalosis in potassium transport in the CCD has not been directly evaluated. When the bath solution was changed from Krebs-Ringer-bicarbonate (KRB) solution to N-2-hydroxyethylpiperazine-NЈ-2-ethanesulfonic acid (HEPES) buffer solution, intracellular pH shifted to alkalosis.…”

Section: Introductionmentioning

confidence: 99%

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Intracellular alkalosis stimulates potassium secretion in rabbit CCD

Tabei¹,

Muto

Furuya

et al. 1999

Clinical and Experimental Nephrology

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Background. Clinically, it is well known that alkalosis induces hypokdemia, but the precise mechanisms of these interactions between acid-base disturbances and potassium homeostasis are not known with certainty. The role of intracellular alkalosis in the regulation of transepithelial potassium transport was examined in rabbit cortical collecting ducts (CCD). Methods. Intracellular alkalosis was induced by 25 mM N-2 hydroxyethylpiperazine-NЈ-2-ethanesulfonic acid (HEPES) buffer in which bicarbonate and CO 2 were eliminated. Intracellular pH (pHi) was measured by the load of 2Ј,7Ј-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) dye in principal cells. Isolated CCD was perfused in vitro, and electrophysiological studies and electrolyte transport studies were performed with or without HEPES buffer. Results. Basal pHi in the Krebs-Ringer-Bicarbonate solution was 7.11 Ϯ 0.06. Alkalization by HEPES buffer solution (pH 7.4) resulted in pHi 7.54 Ϯ 0.16. Intracellular alkalization induced by HEPES solution significantly hyperpolarized transepithelial voltage, while net potassium flux increased from Ϫ17.3 Ϯ 3.6 to Ϫ21.0 Ϯ 3.4 pmol·min Ϫ1 ·mm Ϫ1 . However, lumen-to-bath isotope sodium flux did not change. The basolateral membrane voltage of the principal cells increased from Ϫ74.6 Ϯ 3.0 to Ϫ79.6 Ϯ 2.9 mV and transepithelial resistance decreased significantly from 113.1 Ϯ 2.7 to 100.9 Ϯ 20.1 Ω·cm 2 . The calculated fractional resistance of the apical membrane decreased, indicating that intracellular alkalosis increases apical potassium conductance. In the presence of either basolateral ouabain, luminal amiloride, or luminal barium, the HEPES-induced hyperpolarization was preserved. Conclusion. The present study demonstrates that intracellular pH is an important determinant of apical potassium conductance in CCD. Additionally, it should be noted that in the experiments using HEPES buffer solution, intracellular pH in certain epithelial cells was alkalinized by the elimination of bicarbonate and CO 2 .

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Potassium secretion is inhibited by metabolic acidosis in rabbit cortical collecting ducts in vitro

Cited by 10 publications

References 0 publications

TWIK-2, a New Weak Inward Rectifying Member of the Tandem Pore Domain Potassium Channel Family

TWIK-2, a New Weak Inward Rectifying Member of the Tandem Pore Domain Potassium Channel Family

Conservation of pH sensitivity in the epithelial sodium channel (ENaC) with Liddle's syndrome mutation

Intracellular alkalosis stimulates potassium secretion in rabbit CCD

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