Methyl-[beta]-cyclodextrin reversibly alters the gating of lipid rafts-associated Kv1.3 channels in Jurkat T lymphocytes

• Published in: Pflügers Archiv Vol. 454; no. 2; p. 235
• Main Authors: Pottosin, Igor I, Valencia-cruz, Georgina, Bonales-alatorre, Edgar, Shabala, Sergey N, Dobrovinskaya, Oxana R
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.05.2007
• Subjects: Cells; Lipids
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-007-0208-4

The voltage-dependent Kv1.3 potassium channels mediate a variety of physiological functions in human T lymphocytes. These channels, along with their multiple regulatory components, are localized in cholesterol-enriched microdomains of plasma membrane (lipid rafts). In this study, patch-clamp technique was applied to explore the impact of the lipid-raft integrity on the Kv1.3 channel functional characteristics. T lymphoma Jurkat cells were treated for 1 h with cholesterol-binding oligosaccharide methyl-β-cyclodextrin (MβCD) in 1 or 2 mM concentration, resulting in depletion of cholesterol by 63±5 or 75±4%, respectively. Treatment with 2 mM MβCD did not affect the cells viability but retarded the cell proliferation. The latter treatment caused a depolarizing shift of the Kv1.3 channel activation and inactivation by 11 and 6 mV, respectively, and more than twofold decrease in the steady-state activity at depolarizing potentials. Altogether, these changes underlie the depolarization of membrane potential, recorded in a current-clamp mode. The effects of MβCD were concentration- and time-dependent and reversible. Both development and recovery of the MβCD effects were completed within 1-2 h. Therefore, cholesterol depletion causes significant alterations in the Kv1.3 channel function, whereas T cells possess a potential to reverse these changes.[PUBLICATION ABSTRACT]