Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

pH Regulation in Cells01:28

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Renal Regulation of Acid-Base Balance01:29

Renal Regulation of Acid-Base Balance

Metabolic reactions in the body produce nonvolatile acids, such as sulfuric acid, which generate an acid load of approximately 1 mEq of H+ per kilogram of body weight daily. Excreting H+ in the urine is essential to balance this acid load.
In the kidneys, cells within the proximal convoluted tubules (PCT) and the collecting ducts secrete hydrogen ions (H+) into the tubular fluid. Specifically, in the PCT, Na+/H+ antiporters secrete H+ while reabsorbing Na+.
However, the intercalated cells in...
Enteric Nervous System: Regulation of GI Motor Activity01:11

Enteric Nervous System: Regulation of GI Motor Activity

The Enteric Nervous System (ENS) plays a pivotal role in regulating gastrointestinal or GI motor activity. This complex network of nerves, deeply embedded within the gut wall, responds to changes in the gut environment and receives input from both the autonomic nervous system and the central nervous system. By doing so, the ENS operates various programs tailored to the body's nutritional status and needs.
During periods of fasting, the ENS initiates the migrating myoelectric complex, a program...
pH Homeostasis01:31

pH Homeostasis

Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.
Respiratory Regulation of...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Beat-locked ATP microdomains in the sinoatrial node map a Ca2+-timed energetic hierarchy and regional pacemaker roles.

The Journal of general physiology·2026
Same author

Genetic deletion of ASIC3 alters left ventricular remodeling and autonomic function after myocardial infarction in mice.

Physiological reports·2026
Same author

Potassium channels in vascular smooth muscle cells.

Physiological reviews·2026
Same author

Siglec-E deletion alters AT macrophages phenotypes, induces an inflammatory response, and adipogenesis during diet-induced obesity.

International immunopharmacology·2025
Same author

Discovery of the U2AF1-UHM Inhibitor That Possesses Anti-Leukemia Activity In Vitro.

ACS medicinal chemistry letters·2025
Same author

Genetic Deletion of ASIC3 Alters Left Ventricular Remodeling and Autonomic Function After Myocardial Infarction in Mice.

bioRxiv : the preprint server for biology·2025

Related Experiment Video

Updated: Jun 28, 2026

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments
08:56

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments

Published on: July 5, 2014

Extracellular protons regulate human ENaC by modulating Na+ self-inhibition.

Daniel M Collier1, Peter M Snyder

  • 1Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.

The Journal of Biological Chemistry
|November 8, 2008
PubMed
Summary

Protons alter epithelial sodium channel (ENaC) activity, increasing current in acidic conditions and decreasing it in alkaline conditions. This pH regulation of ENaC occurs by modulating channel gating through altered sodium self-inhibition.

More Related Videos

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane
07:38

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Published on: March 30, 2015

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters
11:51

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters

Published on: February 3, 2018

Related Experiment Videos

Last Updated: Jun 28, 2026

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments
08:56

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments

Published on: July 5, 2014

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane
07:38

Functional Characterization of Na+/H+ Exchangers of Intracellular Compartments Using Proton-killing Selection to Express Them at the Plasma Membrane

Published on: March 30, 2015

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters
11:51

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters

Published on: February 3, 2018

Area of Science:

  • Physiology
  • Molecular Biology
  • Ion Channel Function

Background:

  • The epithelial sodium channel (ENaC) is crucial for sodium transport in organs like the kidney, lung, and sweat ducts.
  • ENaC function is vital for maintaining electrolyte balance and fluid homeostasis.
  • Understanding ENaC regulation by environmental factors like pH is essential for physiological insights.

Purpose of the Study:

  • To investigate the effect of varying pH levels on the activity of the epithelial sodium channel (ENaC).
  • To elucidate the underlying mechanism by which protons modulate ENaC function.
  • To explore potential species-specific differences in ENaC proton sensitivity.

Main Methods:

  • Utilized Xenopus oocytes and H441 epithelial cells expressing human and rat ENaC subunits.
  • Measured amiloride-sensitive currents to quantify ENaC activity under different pH conditions (pH 8.5-6.0).
  • Employed molecular manipulations (mutations, cleavage) and ionic manipulations (Na+ removal) to probe ENaC gating and proton interaction.

Main Results:

  • Acidic pH (below 7.4) increased human ENaC activity, while alkaline pH decreased it, with a pH(50) of 7.2.
  • Proton-induced changes in ENaC activity were observed in human airway epithelia but not in rat ENaC, highlighting species differences primarily in gammaENaC.
  • The effect of pH on ENaC was abolished in channels locked in a high open-probability state, indicating modulation of gating.
  • Protons were found to reduce Na+ self-inhibition, a key regulator of ENaC gating, in a dose-dependent manner.

Conclusions:

  • Protons regulate human ENaC activity by modulating channel gating, specifically by altering the mechanism of Na+ self-inhibition.
  • Species-specific differences exist in proton regulation of ENaC, largely due to variations in the gammaENaC subunit.
  • This pH-dependent regulation of ENaC may play a significant role in facilitating epithelial sodium transport during acidosis.