Cholesterol modifies the gating of Kv1.3 in human T lymphocytes

Péter Hajdú, Zoltán Varga, Carlo Pieri, G. Panyi, R. Gáspár

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The Kv1.3 potassium channel that belongs to the Shaker family of voltage-gated K+ channels plays a crucial role in the mitogenic response of T cells. Because it spans the cell membrane its function can be influenced by lipid-protein interactions. In order to study the effect of lipid-protein interactions on the functioning of Kv1.3 we manipulated the membrane cholesterol content in T cells mimicking various physiological conditions by means of the oligosaccharide methyl-β-cyclodextrin (MβCD) and its cholesterol-saturated complex (MβCD/C). Fluorescence polarization anisotropy and peak current density were used to monitor the efficiency of cholesterol removal (MβCD) and loading (MβCD/C). Using whole-cell patch-clamp technique we determined the kinetic and steady-state parameters of activation and inactivation of the Kv1.3 currents under different treatment conditions. Upon elevation of cholesterol content by 1 or 1.5 mg/ml MβCD/C the rates of both activation and inactivation were slowed. Moreover, the increased cholesterol level in the membrane resulted in a biphasic activation curve. Cholesterol depletion with MβCD (0.95 and 1.425 mg/ml) caused no significant changes in the gating characteristics of Kv1.3. The equilibrium between the open and the closed states of the channels was affected by increased cholesterol content, but at the same time steady-state inactivation was unchanged. We argue that manipulation of membrane cholesterol changed both the kinetic properties of Kv1.3 and steady-state parameters of activation by modifying lipid-protein interactions.

Original languageEnglish
Pages (from-to)674-682
Number of pages9
JournalPflugers Archiv European Journal of Physiology
Volume445
Issue number6
Publication statusPublished - Mar 1 2003

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T-cells
Cyclodextrins
Cholesterol
T-Lymphocytes
Chemical activation
Fluorescence Polarization
Membranes
Lipids
Kv1.3 Potassium Channel
Voltage-Gated Potassium Channels
Proteins
Kinetics
Clamping devices
Patch-Clamp Techniques
Cell membranes
Oligosaccharides
Anisotropy
Current density
Fluorescence
Cell Membrane

Keywords

  • Cholesterol
  • Kv1.3 gating
  • Methyl-β-cyclodextrin
  • T-lymphocyte

ASJC Scopus subject areas

  • Physiology

Cite this

Cholesterol modifies the gating of Kv1.3 in human T lymphocytes. / Hajdú, Péter; Varga, Zoltán; Pieri, Carlo; Panyi, G.; Gáspár, R.

In: Pflugers Archiv European Journal of Physiology, Vol. 445, No. 6, 01.03.2003, p. 674-682.

Research output: Contribution to journalArticle

Hajdú, Péter ; Varga, Zoltán ; Pieri, Carlo ; Panyi, G. ; Gáspár, R. / Cholesterol modifies the gating of Kv1.3 in human T lymphocytes. In: Pflugers Archiv European Journal of Physiology. 2003 ; Vol. 445, No. 6. pp. 674-682.
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