NDLI: Insulin and IGF-1 activate Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage.

Please wait, while we are loading the content...

Insulin and IGF-1 activate Kir4.1/5.1 channels in cortical collecting duct principal cells to control basolateral membrane voltage.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zaika, Oleg Palygin, Oleg Tomilin, Viktor Mamenko, Mykola Staruschenko, Alexander Pochynyuk, Oleh
Description	Author Affiliation: Zaika O ( Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas); Palygin O ( Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin); Tomilin V ( Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas); Mamenko M ( Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas); Staruschenko A ( Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin); Pochynyuk O ( Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, Texas)
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.
File Format	HTM / HTML
ISSN	1931857X
Issue Number	4
Volume Number	310
e-ISSN	15221466
Journal	AJP: Renal Physiology
Language	English
Publisher	American Physiological Society
Publisher Date	2016-02-15
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Research Support, N.i.h., Extramural Cell Membrane Research Support, Non-u.s. Gov't Kidney Tubules, Collecting Male Antagonists & Inhibitors Journal Article Discipline Physiology Hypoglycemic Agents Dose-response Relationship, Drug Patch-clamp Techniques Potassium Channel Blockers Phosphatidylinositol 3-kinases Signal Transduction Potassium Channels, Inwardly Rectifying Mice, Inbred C57bl Discipline Nephrology Pharmacology Metabolism Drug Effects Insulin Insulin-like Growth Factor I Chemistry Animals Agonists Mice Electrophysiological Phenomena
Content Type	Text
Resource Type	Article
Subject	Physiology Urology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in