Regulation of Kv1.3 channels in activated human T lymphocytes by Ca 2+ -dependent pathways

M. C. Chang, R. Khanna, L. C. Schlichter

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Activated T lymphoblasts respond more effectively to mitogenic stimuli than resting T cells, partly through differences in Ca 2+ signaling, which in turn depend on K + channel activity. Both Kv1.3 and Ca 2+ -activated K + (SK4) channels are up-regulated in T lymphoblasts. Since Ca 2+ - and calmodulin (CaM)-dependent signaling are key pathways in T-cell activation, we investigated their involvement in regulating the Kv1.3 current. Kv1.3 in lymphoblasts was significantly inhibited by elevating internal Ca 2+ to the micromolar level. It was also reduced in a Ca 2+ -dependent manner by inhibiting CaM with W-7 or calmidazolium. Part of the CaM-dependence is likely through CaM kinase since the current was also inhibited by the antagonist, KN-62, but not by the inactive analogue, KN-04. Kinase inhibition, unlike CaM inhibition, was only effective at physiological temperatures, a difference that implies involvement of more than one mechanism. We demonstrated a biochemical association of Kv1.3 protein in lymphoblasts with the multifunctional type II CaM kinase, but not with calmodulin. Thus, Kv1.3 forms a multi-protein complex with CaM kinase II (which binds to Ca 2+ /CaM) and previously identified proteins (e.g., PSD-95, src tyrosine kinase) that position the channel to respond to signaling pathways that are crucial for T-cell activation and proliferation.

Original languageEnglish (US)
Pages (from-to)123-134
Number of pages12
JournalCellular Physiology and Biochemistry
Volume11
Issue number3
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • CaM kinase
  • CaM-kinase binding
  • Calmodulin
  • Calmodulin inhibitor
  • K-channel inhibition
  • Kv1.3 regulation
  • T-cell activation

ASJC Scopus subject areas

  • Physiology

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