Lysosome mediated Kir2.1 breakdown directly influences inward rectifier current density

Biochemical and Biophysical Research Communications
John A JansenM A G van der Heyden

Abstract

The inward rectifier current generated by Kir2.1 ion channel proteins is primarily responsible for the stable resting membrane potential in various excitable cell types, like neurons and myocytes. Tight regulation of Kir2.1 functioning prevents premature action potential formation and ensures optimal repolarization times. While Kir2.1 forward trafficking has been addressed in a number of studies, its degradation pathways are thus far unknown. Using three different lysosomal inhibitors, NH(4)Cl, chloroquine and leupeptin, we now demonstrate involvement of the lysosomal degradation pathway in Kir2.1 breakdown. Upon application of the inhibitors, increased steady state protein levels are detectable within few hours coinciding with intracellular granular Kir2.1 accumulation. Treatment for 24h with either chloroquine or leupeptin results in increased plasmamembrane originating inward rectifier current densities, while current-voltage characteristics remain unaltered. We conclude that the lysosomal degradation pathway contributes to Kir2.1 mediated inward rectifier current regulation.

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Citations

Dec 3, 2011·The Journal of Biological Chemistry·Ameet A ChimoteLaura Conforti
Apr 30, 2013·Cardiovascular Research·Hiroki TakanariMarcel A G van der Heyden
Aug 20, 2010·American Journal of Physiology. Cell Physiology·Corina M BalutDaniel C Devor
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Nov 30, 2012·Pflügers Archiv : European journal of physiology·Rosanne VarkevisserMarcel A G van der Heyden
Feb 19, 2016·Pflügers Archiv : European journal of physiology·Alejandra G PalmaGabriela I Marino
Feb 21, 2016·Pharmacology & Therapeutics·Susumu OhyaKatsuhiko Muraki
Feb 8, 2011·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Marcel A G van der Heyden, José A Sánchez-Chapula
Sep 11, 2010·The Journal of Surgical Research·Claudio MuscariCarlo Guarnieri
Apr 6, 2013·Pharmacology & Therapeutics·Kathy C G de GitMarcel A G van der Heyden
May 29, 2016·Biochemical and Biophysical Research Communications·Hideto YamamuraYuji Imaizumi
Jun 5, 2016·Toxicology and Applied Pharmacology·Yea Lu TayMei Lan Tan
Apr 21, 2017·Journal of Cellular and Molecular Medicine·Yuan JiMarcel A G van der Heyden
Dec 19, 2009·American Journal of Physiology. Cell Physiology·Elyssa D BurgJason X-J Yuan
Nov 17, 2019·Biomolecules·Eva-Maria Zangerl-PlesslMarcel A G van der Heyden
Dec 31, 2008·The Journal of Biological Chemistry·David PerozJean Mérot
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Jul 25, 2019·Frontiers in Physiology·Muge QileMarcel A G van der Heyden
Jun 14, 2013·American Journal of Physiology. Renal Physiology·Donghai WenSteven C Sansom
Jun 23, 2020·International Journal of Antimicrobial Agents·Kanigula Mubagwa

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