4.5 Review

Characteristics and Pharmacological Regulation of Epithelial Na+ Channel (ENaC) and Epithelial Na+ Transport

Journal

JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 126, Issue 1, Pages 21-36

Publisher

JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.14R01SR

Keywords

epithelial Na+ channel (ENaC); epithelial Na+ transport; chloride ion; electrophysiology; epithelium

Funding

  1. National Kidney Foundation of the USA
  2. Heart and Stroke Foundation of Canada
  3. Medical Research Council of Canada
  4. National Sanatorium Foundation of Canada
  5. Ontario Thoracic Society (Canada)
  6. Kidney Foundation of Canada
  7. Premier's Research Excellence Award (Canada)
  8. Japan Society of The Promotion of Science [13670046, 15590189, 15659052, 17390057, 17590191, 19590212, 20390060, 237645, 25670111]
  9. Salt Science Research Foundation [0143, 0241, 0736, 0837, 1035, 1122, 1235]
  10. Research Conference for Cell Function
  11. Fuji Foundation for Protein Research
  12. Kyoto Innovation Collaboration Center
  13. Yamada Research Grant
  14. KIT-KPUM-KPU-KPhU Collaborative Research Program
  15. Adaptable and Seamless Technology Transfer Program through Target-Driven R&D, Japan Science and Technology (JST) Agency
  16. Grants-in-Aid for Scientific Research [13670046, 17590191, 15659052, 17390057, 15590189] Funding Source: KAKEN

Ask authors/readers for more resources

Epithelial Na+ transport participates in control of various body functions and conditions: e.g., homeostasis of body fluid content influencing blood pressure, control of amounts of fluids covering the apical surface of alveolar epithelial cells at appropriate levels for normal gas exchange, and prevention of bacterial/viral infection. Epithelial Na+ transport via the transcellular pathway is mediated by the entry step of Na+ across the apical membrane via Epithelial Na+ Channel (ENaC) located at the apical membrane, and the extrusion step of Na+ across the basolateral membrane via the Na+,K+-ATPase located at the basolateral membrane. The rate-limiting step of the epithelial Na+ transport via the transcellular pathway is generally recognized to be the entry step of Na+ across the apical membrane via ENaC. Thus, up-/down-regulation of ENaC essentially participates in regulatory systems of blood pressure and normal gas exchange. Amount of ENaC-mediated Na+ transport is determined by the number of ENaCs located at the apical membrane, activity (open probability) of individual ENaC located at the apical membrane, single channel conductance of ENaC located at the apical membrane, and driving force for the Na+ entry via ENaCs across the apical membrane. In the present review article, I discuss the characteristics of ENaC and how these factors are regulated.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Oncology

ANO9 Regulated Cell Cycle in Human Esophageal Squamous Cell Carcinoma

Keita Katsurahara, Atsushi Shiozaki, Toshiyuki Kosuga, Michihiro Kudou, Katsutoshi Shoda, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eiichi Konishi, Yoshinori Marunaka, Eigo Otsuji

ANNALS OF SURGICAL ONCOLOGY (2020)

Review Cell Biology

Roles of Ion and Water Channels in the Cell Death and Survival of Upper Gastrointestinal Tract Cancers

Atsushi Shiozaki, Yoshinori Marunaka, Eigo Otsuji

Summary: Ion and water channels play a role in the function of cancer cells, including esophageal and gastric cancer cells. The expression and regulation of these channels and transporters could be potential targets for cancer management.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Review Biochemistry & Molecular Biology

Roles of interstitial fluid pH and weak organic acids in development and amelioration of insulin resistance

Yoshinori Marunaka

Summary: Type 2 diabetes mellitus is a common lifestyle-related disease caused by overeating and lack of exercise, leading to metabolic disorders. Hyperglycemia and insulin resistance are main symptoms, with the instability of interstitial fluid pH potentially affecting insulin binding affinity.

BIOCHEMICAL SOCIETY TRANSACTIONS (2021)

Article Biophysics

Plasma membrane anchored nanosensor for quantifying endogenous production of H2O2 in living cells

Shigekuni Hosogi, Yoshinori Marunaka, Eishi Ashihara, Tadaaki Yamada, Ayumi Sumino, Hideo Tanaka, Leonardo Puppulin

Summary: A newly designed nanosensor anchored to the outer cell surface can quantify H2O2 at nanometer distance, providing important information for studying cell signaling. The nanosensor is built upon gold nanoparticles functionalized with a H2O2-sensitive boronate compound and probed using surface enhanced Raman spectroscopy (SERS).

BIOSENSORS & BIOELECTRONICS (2021)

Article Biochemistry & Molecular Biology

Essential requirement of complex number for oscillatory phenomenon in intracellular trafficking process

Yoshinori Marunaka, Katsumi Yagi

Summary: This study investigates the intracellular protein trafficking processes using mathematical equations, exploring the implications of real and complex roots on the protein quantities in different states. Real roots correspond to monotonic changes, while complex roots lead to oscillatory changes, indicating the essential role of complex numbers in oscillatory phenomena in bodily and cellular functions.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2021)

Article Physiology

Nitric oxide synthesis stimulated by arachidonic acid accumulation via PPARα in acetylcholine-stimulated gastric mucous cells

Saori Tanaka, Shigenori Ito, Chikao Shimamoto, Hitoshi Matsumura, Toshio Inui, Yoshinori Marunaka, Takashi Nakahari

Summary: This study demonstrates that NO production is enhanced by AA via PPAR alpha in ACh-stimulated antral mucous cells, and the production of AA is regulated by cPLA2 activation. Additionally, indomethacin enhances Ca2+-regulated exocytosis by increasing NO synthesis through PPAR alpha activation.

EXPERIMENTAL PHYSIOLOGY (2021)

Article Endocrinology & Metabolism

Metabolic functions of flavonoids: From human epidemiology to molecular mechanism

Wataru Aoi, Masayo Iwasa, Yoshinori Marunaka

Summary: Dietary flavonoid intake is associated with the regulation of nutrient metabolism and has been shown to lower the risk of metabolic and cardiovascular diseases. Studies have also demonstrated that flavonoids can improve energy expenditure and glucose tolerance. Furthermore, some flavonoids may regulate thermogenesis and feeding behavior through modulating the autonomic and central nervous systems.

NEUROPEPTIDES (2021)

Article Biochemistry & Molecular Biology

Possibility of Venous Serum Cl- Concentration ([Cl-]s) as a Marker for Human Metabolic Status: Correlation of [Cl-]s to Age, Fasting Blood Sugar (FBS), and Glycated Hemoglobin (HbA1c)

Yoshinori Marunaka, Katsumi Yagi, Noboru Imagawa, Hironori Kobayashi, Masaru Murayama, Asami Minamibata, Yoshiaki Takanashi, Takashi Nakahari

Summary: The study suggests that serum Cl- concentration may be a more effective marker for detecting metabolic conditions compared to HCO3- concentration. Cl- concentration is positively correlated with age and negatively correlated with FBS and HbA1c, especially in individuals with high FBS/HbA1c levels.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Cell Biology

Ezrin knockdown reduces procaterol-stimulated ciliary beating without morphological changes in mouse airway cilia

Kotoku Kawaguchi, Shogo Nakayama, Daichi Saito, Haruka Kogiso, Kasane Yasuoka, Yoshinori Marunaka, Takashi Nakahari, Shinji Asano

Summary: Mucociliary clearance is a major defense mechanism of the airway epithelium, and ezrin plays an important role in regulating the beating of airway ciliary cells by promoting the apical surface localization of β(2)AR.

JOURNAL OF CELL SCIENCE (2022)

Article Biochemistry & Molecular Biology

Minimum biological domain of xenin-25 required to induce anion secretion in the rat ileum

Yuko Kuwahara, Kohei Takahashi, Miho Akai, Ikuo Kato, Takaharu Kozakai, Shinji Asano, Toshio Inui, Yoshinori Marunaka, Atsukazu Kuwahara

Summary: Xenin-25 has various physiological functions in the gastrointestinal tract, including ion transport and motility. It shows sequence homology with neurotensin, and the minimal biological domain required for inducing ion transport in the rat ileum contains the C-terminal pentapeptide. Furthermore, Arg at position 21 is crucial for retaining the biological activity of Xenin-25.

PEPTIDES (2022)

Article Multidisciplinary Sciences

Detection and categorization of severe cardiac disorders based solely on heart period measurements

Shigeru Shinomoto, Yasuhiro Tsubo, Yoshinori Marunaka

Summary: Cardiac disorders are common and serious, so continuous monitoring of cardiac status is crucial. A newly developed automated system for alerting individuals about cardiac disorders solely by measuring heart periods is described in this paper. The study found that local variation metric is more efficient than conventional heart rate variability metrics for alerting cardiac disorders, and a newly introduced local-global variation metric has superior capacity for discriminating between different types of cardiac problems.

SCIENTIFIC REPORTS (2022)

Article Environmental Sciences

Association between 3-Year Repetitive Isolated Hematuria and eGFR Deterioration in an Apparently Healthy Population: A Retrospective Cohort Study

Mami Ishida, Keiichi Matsuzaki, Hitoshi Suzuki, Yusuke Suzuki, Takashi Kawamura, Yoshinori Marunaka, Taku Iwami

Summary: Persistent hematuria is associated with the presence of hematuria and proteinuria suggestive of glomerulonephritis, but not with eGFR deterioration. Higher frequency of preceding hematuria is associated with a greater risk of hematuria 5 years later.

INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH (2022)

Review Biochemistry & Molecular Biology

Molecular Mechanisms of Obesity-Induced Development of Insulin Resistance and Promotion of Amyloid-β Accumulation: Dietary Therapy Using Weak Organic Acids via Improvement of Lowered Interstitial Fluid pH

Yoshinori Marunaka

Summary: Insulin resistance is a factor in the development of type 2 diabetes and Alzheimer's disease. Understanding the mechanisms of insulin resistance is crucial for preventing these diseases. The body's pH environment plays a role in regulating hormone action and maintaining homeostasis. Diet therapies can improve insulin resistance by raising the pH of interstitial fluid with weak organic acids and promoting their absorption in the gut.

BIOMOLECULES (2023)

Review Physiology

Physiological roles of chloride ions in bodily and cellular functions

Yoshinori Marunaka

Summary: This article reviews the various roles of Cl- in the body, including its involvement in cellular functions, cell proliferation, taste receptors, ciliary motility, and its relationship with H+.

JOURNAL OF PHYSIOLOGICAL SCIENCES (2023)

Article Physiology

The effect of Xenin25 on spontaneous circular muscle contractions of rat distal colon in vitro

Yuko Kuwahara, Ikuo Kato, Toshio Inui, Yoshinori Marunaka, Atsukazu Kuwahara

Summary: Xenin25 has an inhibitory effect on the spontaneous circular muscle contractions in the rat distal colon, with postinhibitory spontaneous contractions at a higher frequency. The mechanism involves activation of neuronal NTSR1, transmitters from VIP and apamin-sensitive NO neurons, and NK1R to modulate the muscle contractions. Xenin25 is considered an important modulator of postprandial circular muscle contraction in the distal colon.

PHYSIOLOGICAL REPORTS (2021)

No Data Available