Resting Potential and Ion Movements in the Frog Skin

Levi, Hilde; Ussing, Hans H.

doi:10.1038/164928a0

Cited by 47 publications

(14 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…External pH Ͻ 5 decreased short-circuit current in frog skin (26) but increased Na ϩ transport in toad bladder (27). In cultured Xenopus collecting duct cells (A6), acidification of the extracellular medium (pH 6.4 and 5.4) produced a slow increase in amiloride-sensitive current that peaked at ϳ30 min (28).…”

mentioning

confidence: 99%

Extracellular Protons Regulate Human ENaC by Modulating Na+ Self-inhibition

Collier

Snyder

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

The epithelial Na ؉ channel, ENaC, is exposed to a wide range of proton concentrations in the kidney, lung, and sweat duct. We, therefore, tested whether pH alters ENaC activity. In Xenopus oocytes expressing human ␣-, ␤-, and ␥ENaC, amiloridesensitive current was altered by protons in the physiologically relevant range (pH 8.5-6.0). Compared with pH 7.4, acidic pH increased ENaC current, whereas alkaline pH decreased current (pH 50 ‫؍‬ 7.2). Acidic pH also increased ENaC current in H441 epithelia and in human primary airway epithelia. In contrast to human ENaC, pH did not alter rat ENaC current, indicating that there are species differences in ENaC regulation by protons. This resulted predominantly from species differences in ␥ENaC. Maneuvers that lock ENaC in a high open-probability state ("DEG" mutation, proteolytic cleavage) abolished the effect of pH on human ENaC, indicating that protons alter ENaC current by modulating channel gating. Previous work showed that ENaC gating is regulated in part by extracellular Na ؉ ("Na ؉ self-inhibition"). Based on several observations, we conclude that protons regulate ENaC by altering Na ؉ self-inhibition. First, protons reduced Na ؉ self-inhibition in a dose-dependent manner. Second, ENaC regulation by pH was abolished by removing Na ؉ from the extracellular bathing solution. Third, mutations that alter Na ؉ self-inhibition produced corresponding changes in ENaC regulation by pH. Together, the data support a model in which protons modulate ENaC gating by relieving Na ؉ self-inhibition. We speculate that this may be an important mechanism to facilitate epithelial Na ؉ transport under conditions of acidosis.

show abstract

mentioning

confidence: 99%

Extracellular Protons Regulate Human ENaC by Modulating Na+ Self-inhibition

Collier

Snyder

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…I found, however, that the clinicians at the Donner Lab used large amounts of isotopes, notably 24Na and l3lI, for treating patients;--by rinsing their empty bottles I recovered plenty of tracer material for my own work. Thus I was able to illustrate the usefulness of the fl ux ratio equation by showing that iodide behaved as a passive ion when passing the frog skin whereas sodium moved almost exclusively by active transport (16).…”

Section: The Flux Ratio Equationmentioning

confidence: 99%

Life with Tracers

Ussing¹

1980

Annu. Rev. Physiol.

Self Cite

View full text Add to dashboard Cite

“…2, it would seem that at a voltage of 30 to 40 inv., K + is neither rejected by nor taken up by the epithelium. Using the tracer technic, Levi and Ussing (15) have found that at about 50 my., influx and out.flux of tracer potassium are equal. These authors also suggested the possibility of active K + uptake by the epithelium of skin.…”

Section: K + Rejection--according To Linderholm (16) the Net Transpomentioning

confidence: 99%

The Relationship of Sodium Uptake, Potassium Rejection, and Skin Potential in Isolated Frog Skin

Huf

Wills

1953

Journal of General Physiology

View full text Add to dashboard Cite

1. Isolated surviving frog skin, when bathed with the same kind of diluted Ringer's solution on both sides, shows a negative correlation between net active salt uptake by the epithelium and spontaneous skin potential. Average values of 0.15 to 0.86 µeq. x hr.–1 x cm.–2 were measured and correlated with average skin potentials ranging from 107 to 25 mv. 2. Sodium uptake exceeded chloride uptake by about the same amount, irrespective of the height of the skin potential. 3. The same skins which exhibited a negative correlation between net uptake of sodium chloride and skin potential showed a positive correlation between net potassium rejection from the epithelium and skin potential, for voltages above 30 to 40 mv. In skins of voltages lower than this, potassium ions were taken up rather than rejected. Average values for rejection of +11.8 to –0.8 centi-µeq. x hr.–1 x cm.–2 were measured. 4. Net fluid uptake, associated with active uptake of sodium chloride, was small and occurred in the direction of the salt uptake. No dependence of net fluid uptake upon skin potential was observed. 5. Skins of winter frogs, pretreated with a commercial purified ACTH preparation, were less active than their respective controls with regard to uptake of sodium chloride. Rejection of potassium was the same in treated and untreated skins. Posterior pituitary factors, as possible contaminants, did not account for the effect of the ACTH preparation. 6. DOCA, DOC, and cortisone did not alter the normal correlation referred to under (1) and (3). 7. In interpreting the experimental results on theoretical grounds, it is suggested (a) that in normal skin, it is the variation in the electric conductance in skin of chloride ions which essentially, although not exclusively, determines the rate of net uptake of sodium chloride, (b) that a factor in the ACTH preparation used, possibly ACTH itself, may have lowered the electric conductance in skin of sodium ions either truly or apparently, (c) that potassium ions are treated by the skin primarily as passive ions. There is some indication that potassium ions are also actively taken up by the epithelium of skin.

show abstract

Resting Potential and Ion Movements in the Frog Skin

Cited by 47 publications

References 2 publications

Extracellular Protons Regulate Human ENaC by Modulating Na+ Self-inhibition

Extracellular Protons Regulate Human ENaC by Modulating Na+ Self-inhibition

Life with Tracers

The Relationship of Sodium Uptake, Potassium Rejection, and Skin Potential in Isolated Frog Skin

Contact Info

Product

Resources

About