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

Sándor Somodi, Péter Hajdu, R. Gáspár, G. Panyi, Zoltán Varga

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 Ba2+ ions from the extracellular space to the control site was significantly slowed by low pH e in wild-type hKv1.3, but it was insensitive to pHe 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 control site in both directions and the effect on inactivation rate (acceleration or slowing) depends on the relative contribution of filling from the extracellular and intracellular sides.

Original languageEnglish
Pages (from-to)1145-1156
Number of pages12
JournalEuropean Biophysics Journal
Volume37
Issue number7
DOIs
Publication statusPublished - Sep 2008

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Histidine
Potassium
Ions
Extracellular Space
Binding Sites

Keywords

  • Barium block
  • Extracellular K concentration
  • Extracellular pH
  • Inactivation
  • K binding site
  • Potassium channel

ASJC Scopus subject areas

  • Biophysics

Cite this

Effects of changes in extracellular pH and potassium concentration on Kv1.3 inactivation. / Somodi, Sándor; Hajdu, Péter; Gáspár, R.; Panyi, G.; Varga, Zoltán.

In: European Biophysics Journal, Vol. 37, No. 7, 09.2008, p. 1145-1156.

Research output: Contribution to journalArticle

Somodi, Sándor ; Hajdu, Péter ; Gáspár, R. ; Panyi, G. ; Varga, Zoltán. / Effects of changes in extracellular pH and potassium concentration on Kv1.3 inactivation. In: European Biophysics Journal. 2008 ; Vol. 37, No. 7. pp. 1145-1156.
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