Patch-clamp study of cultured human sweat duct cells: amiloride-blockable Na+ channel

Joris, L.; Krouse, Mauri E.; Hagiwara, Grace; Bell, C. L.; Wine, Jeffrey J.

doi:10.1007/bf00584641

Cited by 35 publications

(8 citation statements)

References 6 publications

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“…This generally accepted I-V relationship of amiloride-sensitive Na transport is in contrast to the observation in the present study and suggests that the electrogenic Na transport in sheep rumen, which is amiloride-insensitive (30) and modulated by apical divalent cations (24), is a distinct Na pathway. However, it should be mentioned that a voltage-sensitive (the open probability increases with depolarization) amiloride-blockable Na channel has been described in cultured human sweat duct cells (21) and in A6 cells (16). Recently, Marunaka et al (32) have reported an amiloride-sensitive Na-permeable nonselective cation channel in the apical membrane of fetal alveolar epithelium with an increased open probability when the apical membrane is depolarized.…”

Section: G613mentioning

confidence: 99%

Na transport in sheep rumen is modulated by voltage-dependent cation conductance in apical membrane

Lang

Martens

1999

American Journal of Physiology-Gastrointestinal and Liver Physi

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The effects of clamping the transepithelial potential difference (PDt; mucosa reference) have been studied in sheep rumen epithelium. Pieces of ruminal epithelium were examined in Ussing chambers, in a part of the experiments combined with conventional intracellular recordings. After equilibration, the tissue conductance ( G t) was 2.50 ± 0.09 mS/cm2, the potential difference of the apical membrane (PDa) was −47 ± 2 mV, and the fractional resistance of the apical membrane (f R a) was 68 ± 2% under short-circuit conditions. Hyperpolarization of the tissue (bloodside positive) depolarized PDa, decreased f R a, and increased G tsignificantly. Clamping PDt at negative values caused converse effects on PDa and f R a. All changes were completely reversible. The determination of individual conductances revealed that the conductance of the apical membrane increased almost linearly with depolarization of PDa. The PD-dependent changes were significantly reduced by total replacement of Na. These observations support the assumption of a PD-dependent conductance in the apical membrane that permits enhanced apical uptake of Na even at depolarized PDa. This mechanism appears to be important for the regulation of osmotic pressure in forestomach fluid.

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Section: G613mentioning

confidence: 99%

Na transport in sheep rumen is modulated by voltage-dependent cation conductance in apical membrane

Lang

Martens

1999

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In the sweat gland, the proximal tubule or secretory coil secretes an isoosmotic fluid which is then presented to the water impermeable apical membrane of the distal, reabsorptive tubule or excretory duct (28). No evidence for an amiloride-sensitive conductance was obtained in cultured human sweat gland secretory cells (17), whereas there is evidence for such sodium conductance in excretory ducts (2,13). Patch clamp study of cultured human sweat gland excretory duct provided evidence for an amiloride-sensitive (1 raM) sodium channel that was, however, characterized by a relatively high single channel conductance (15 pS) and was moderately selective (PN,/PK about 4) (13).…”

Section: Cellular Expression Of ~ ~ ~/ Renac Correlates With the Electrogenic Sodium Transport In Aldosterone-responsive Epitheliamentioning

confidence: 99%

Cell-specific expression of epithelial sodium channel alpha, beta, and gamma subunits in aldosterone-responsive epithelia from the rat: localization by in situ hybridization and immunocytochemistry.

Duc

Farman

Canessa

et al. 1994

The Journal of Cell Biology

356

236

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Abstract. A highly selective, amiloride-sensitive, epithelial sodium channel from rat colon (rENaC), composed of three homologous subunits termed ~, /3, and 3" rENaC, has been cloned by functional expression and was proposed to mediate electrogenic sodium reabsorption in aldosterone-responsive epithelia. To determine whether rENaC could account for sodium absorption in vivo, we studied the cellular localization of the sodium channel messenger RNA subunits by in situ hybridization and their cellular and subcellular distribution by immunocytochemistry in the kidney, colon, salivary, and sweat glands of the rat. In the kidney, we show that the three subunit mRNAs are specifically co-expressed in the renal distal convoluted tubules (DCT), connecting tubules (CNT), cortical collecting ducts (CCD), and outer medullary collecting ducts (OMCD), but not in the inner medullary collecting ducts (IMCD). We demonstrate co-localization of or, 8, and 3' subunit proteins in the apical membrane of a majority of cells of CCD and OMCD. Our data indicate that c~,/3, and 3' subunit mRNAs and proteins are co-expressed in the distal nephron (excepting IMCD), a localization that correlates with the previously described physiological expression of amiloride-sensitive electrogenic sodium transport. Our data, however, suggest that another sodium transport protein mediates electrogenic amiloride-sensitive sodium reabsorption in IMCD. We also localized rENaC to the surface epithelial cells of the distal colon and to the secretory ducts of the salivary gland and sweat gland, providing further evidence consistent with the hypothesis that the highly selective, amiloride-sensitive sodium channel is physiologically expressed in aldosterone-responsive cells.XLORIDE-sensitive electrogenic transepithelial sodium transport constitutes the rate limiting step for sodium reabsorption in the epithelium of the distal nephron, the distal colon, the ducts of several exocrine glands (for instance the salivary glands and the sweat glands) and the epithelia of the lung (10). In kidney (25) and colon (29), electrogenic sodium transport is upregulated by aldosterone, a mineralocorticoid hormone, allowing the maintenance of sodium balance, blood volume, and blood pressure (30). In the distal nephron of rats submitted to a 1 wk salt restriction, the electrogenic sodium transport is highly efficient at reabsorbing sodium from the urine of collecting ducts, decreasing luminal sodium concentration to levels as low as 1 raM, while the plasma concentration is maintained at 140 raM. To establish such a gradient, the epithelia of the distal nephron expresses an electrogenic sodium transport mediated by an amiloride-sensitive sodium channel located in the apical membrane facing the external compartment (urine), and a ouabain-sensitive sodium pump restricted to the basolateral membrane facing the extracellular compartment (blood). Current physiological evidence indicates that the amiloride-sensitive epithelial sodium channel is mainly expressed in tissues that fall into t...

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“…Amiloride, a potassium‐sparing diuretic, is used clinically for the management of renal failure, 1 hypertension 2 and congestive heart failure 3 and experimentally as a pharmacological agent 4–6 . Amiloride exerts its effects by blocking Na + channels with high affinity 7,8 and H + channels 9 . Its effects are also mediated bys inhibition of Na + ‐related transporters, such as the Na + –Ca 2+ exchanger, 10 the Na + –H + antiporter 11 and the T‐ or ‐type Ca 2+ channel 12,13 at higher concentrations.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of amiloride on the current mediated by native GABA_A receptors in cultured neurons of rat inferior colliculus

Liu

Zhang

Tang

et al. 2010

Clin Exp Pharma Physio

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1. The diuretic amiloride is known to modulate the activity of several types of ion channels and membrane receptors in addition to its inhibitory effects on many ion transport systems. However, the effects of amiloride on some important ion channels and receptors, such as GABA(A) receptors, in the central nervous system have not been characterized. 2. In the present study, we investigated the functional action of amiloride on native GABA(A) receptors in cultured neurons of rat inferior colliculus using whole-cell patch-clamp recordings. 3. Amiloride reversibly inhibited the amplitude of the GABA-induced current (I(GABA)) in a concentration-dependent manner (IC(50) 454 +/- 24 micromol/L) under conditions of voltage-clamp with a holding potential at -60 mV. The inhibition depended on drug application mode and was independent of membrane potential. Amiloride did not change the reversal potential of I(GABA). Moreover, amiloride induced a parallel right-ward shift in the concentration-response curve for I(GABA) without altering the maximal value and Hill coefficient. 4. The present study shows that amiloride competitively inhibits the current mediated by native GABA(A) receptors in the brain region, probably via a direct action on GABA-binding sites on the receptor. The findings suggest that the functional actions of amiloride on GABA(A) receptors may result in possible side-effects on the central nervous system in the case of direct application of this drug into the cerebrospinal fluid for treatment of diseases such as brain tumours.

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Patch-clamp study of cultured human sweat duct cells: amiloride-blockable Na+ channel

Cited by 35 publications

References 6 publications

Na transport in sheep rumen is modulated by voltage-dependent cation conductance in apical membrane

Na transport in sheep rumen is modulated by voltage-dependent cation conductance in apical membrane

Cell-specific expression of epithelial sodium channel alpha, beta, and gamma subunits in aldosterone-responsive epithelia from the rat: localization by in situ hybridization and immunocytochemistry.

Inhibitory effects of amiloride on the current mediated by native GABA_A receptors in cultured neurons of rat inferior colliculus

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Patch-clamp study of cultured human sweat duct cells: amiloride-blockable Na+ channel

Cited by 35 publications

References 6 publications

Na transport in sheep rumen is modulated by voltage-dependent cation conductance in apical membrane

Na transport in sheep rumen is modulated by voltage-dependent cation conductance in apical membrane

Cell-specific expression of epithelial sodium channel alpha, beta, and gamma subunits in aldosterone-responsive epithelia from the rat: localization by in situ hybridization and immunocytochemistry.

Inhibitory effects of amiloride on the current mediated by native GABAA receptors in cultured neurons of rat inferior colliculus

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Inhibitory effects of amiloride on the current mediated by native GABA_A receptors in cultured neurons of rat inferior colliculus