Effects of changes in extracellular pH and potassium concentration on Kv1.3 inactivation.

European Biophysics Journal : EBJ
Sándor SomodiZoltán Varga

Abstract

The Kv1.3 channel inactivates via the P/C-type mechanism, which is influenced by a histidine residue in the pore region (H399, equivalent of Shaker 449). Previously we showed that the electric field of the protonated histidines at low extracellular pH (pHe) creates a potential barrier for K+ ions just outside the pore that hinders their exit from the binding site controlling inactivation (control site) thereby slowing inactivation kinetics. Here we examined the effects of extracellular potassium [K+]e and pHe on the rate of inactivation of Kv1.3 using whole-cell patch-clamp. We found that in 150 mM [K+]e inactivation was accelerated upon switching to pHe 5.5 as opposed to the slowing at 5 mM [K+]e. The transition from slowing to acceleration occurred at 40 mM [K+]e, whereas this "turning point" was at 20 mM [K+]e for inward currents. The rate of entry of Ba(2+) ions from the extracellular space to the control site was significantly slowed by low pHe in wild-type hKv1.3, but it was insensitive to pH(e) in H399K and H399L mutants. Based on these observations we expanded our model and propose that the potential barrier created by the protonated histidines impedes the passage of K+ ions between the extracellular medium and the cont...Continue Reading

References

Sep 30, 1991·Biochemical and Biophysical Research Communications·A E BuschM P Kavanaugh
Jun 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·K L ChoiG Yellen
Jun 1, 1989·The Journal of Physiology·C Deutsch, S C Lee
Apr 1, 1989·The Journal of General Physiology·S Grissmer, M D Cahalan
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C Deutsch, L Q Chen
Apr 17, 1998·Biophysical Journal·R E HarrisE Y Isacoff
Oct 6, 1998·The Journal of General Physiology·E Loots, E Y Isacoff
Jun 17, 1999·Pflügers Archiv : European journal of physiology·P Pérez-Cornejo
Jun 29, 1999·Quarterly Reviews of Biophysics·G Yellen
Oct 31, 2000·The Journal of General Physiology·E Loots, E Y Isacoff
Sep 13, 2002·American Journal of Physiology. Cell Physiology·T W ClaydonC H Orchard
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Xiaoyan LiRandall L Rasmusson
Aug 16, 2003·Pflügers Archiv : European journal of physiology·John G StarkusStefan H Heinemann
Jun 18, 2004·American Journal of Physiology. Cell Physiology·Sándor SomodiGyörgy Panyi
Aug 25, 2004·Biophysical Journal·Payam AndalibStephen J Korn
Jul 29, 2005·Cell Biochemistry and Biophysics·Shetuan ZhangDavid Fedida
Sep 8, 2006·American Journal of Physiology. Cell Physiology·Cyrus EduljeeSteven J Kehl
May 2, 2007·The Journal of General Physiology·Thomas W ClaydonDavid Fedida

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Citations

May 28, 2013·Pflügers Archiv : European journal of physiology·Yen May ChengSteven J Kehl
Jun 10, 2016·American Journal of Physiology. Cell Physiology·N E FaragM R Boyett
Apr 13, 2021·Frontiers in Pharmacology·Verena HofschröerAlbrecht Schwab

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