ArticleAmerican journal of physiology. Renal physiology2016
Insulin and IGF-1 activate Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage.
Article in American journal of physiology. Renal physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure.European journal of heart failure · 2021Trial
- Inflammation and vasopressin hypersecretion in aging.Frontiers in endocrinology · 2025Review
- Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Review
- Yigan Mingmu Decoction inhibits diabetic macular edema through regulating Kir4.1/AQP4 axis: a study based on network pharmacology.American journal of translational research · 2023Article
- Kir5.1 channels: potential role in epilepsy and seizure disorders.American journal of physiology. Cell physiology · 2022Review
- Inwardly rectifying KAmerican journal of physiology. Cell physiology · 2022Review
- Crosstalk between epithelial sodium channels (ENaC) and basolateral potassium channels (KBritish journal of pharmacology · 2022Article
- ClC-K2 ClFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Kir4.1 may represent a novel therapeutic target for diabetic retinopathy (Review).Experimental and therapeutic medicine · 2021Review
- Deletion of Kir5.1 abolishes the effect of high NaAmerican journal of physiology. Renal physiology · 2021Article
- Inwardly rectifying potassium channel 5.1: Structure, function, and possible roles in diseases.Genes & diseases · 2021Review
- Deletion of renal Nedd4-2 abolishes the effect of high sodium intake (HS) on Kir4.1, ENaC, and NCC and causes hypokalemia during high HS.American journal of physiology. Renal physiology · 2021Article
- Adenosine inhibits the basolateral ClAmerican journal of physiology. Renal physiology · 2020Article
- Expression, localization, and functional properties of inwardly rectifying KAmerican journal of physiology. Renal physiology · 2020Review
- Postprandial effects on electrolyte homeostasis in the kidney.American journal of physiology. Renal physiology · 2019Review
- Postprandial Effects on ENaC-Mediated Sodium Absorption.Scientific reports · 2019Article
- Physiological hyperinsulinemia caused by acute hyperglycemia minimizes renal sodium loss by direct action on kidneys.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Distal tubule basolateral potassium channels: cellular and molecular mechanisms of regulation.Current opinion in nephrology and hypertension · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Potassium Kir4.1/5.1 channels are abundantly expressed at the basolateral membrane of principal cells in the cortical collecting duct (CCD), where they are thought to modulate transport rates by controlling transepithelial voltage. Insulin and insulin-like growth factor-1 (IGF-1) stimulate apically localized epithelial sodium channels (ENaC) to augment sodium reabsorption in the CCD. However, little is known about their actions on potassium channels localized at the basolateral membrane. In this study, we implemented patch-clamp analysis in freshly isolated murine CCD to assess the effect of these hormones on Kir4.1/5.1 at both single channel and cellular levels. We demonstrated that K(+)-selective conductance via Kir4.1/5.1 is the major contributor to the macroscopic current recorded from the basolateral side in principal cells. Acute treatment with 10 μM amiloride (ENaC blocker), 100 nM tertiapin-Q (TPNQ; ROMK inhibitor), and 100 μM ouabain (Na(+)-K(+)-ATPase blocker) failed to produce a measurable effect on the macroscopic current. In contrast, Kir4.1 inhibitor nortriptyline (100 μM), but not fluoxetine (100 μM), virtually abolished whole cell K(+)-selective conductance. Insulin (100 nM) markedly increased the open probability of Kir4.1/5.1 and nortriptyline-sensitive whole cell current, leading to significant hyperpolarization of the basolateral membrane. Inhibition of the phosphatidylinositol 3-kinase cascade with LY294002 (20 μM) abolished action of insulin on Kir4.1/5.1. IGF-1 had similar stimulatory actions on Kir4.1/5.1-mediated conductance only when applied at a higher (500 nM) concentration and was ineffective at 100 nM. We concluded that both insulin and, to a lesser extent, IGF-1 activate Kir4.1/5.1 channel activity and open probability to hyperpolarize the basolateral membrane, thereby facilitating Na(+) reabsorption in the CCD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.