CRAC channels: Activation, permeation, and the search for a molecular identity

Murali Prakriya, Richard S. Lewis*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

142 Scopus citations

Abstract

The Ca2+ release-activated Ca2+ (CRAC) channel is a highly Ca2+ -selective store-operated channel that is expressed in T lymphocytes, mast cells, and other hematopoietic cells. In T cells, CRAC channels are essential for generating the prolonged intracellular Ca2+ ([Ca2+]i) elevation required for the expression of T-cell activation genes. Here we review recent work addressing CRAC channel regulation, pore properties, and the search for CRAC channel genes. Of the current models for CRAC current (ICRAC) activation, several new studies argue against a conformational coupling mechanism in which IP3 receptors communicate store depletion to CRAC channels through direct physical interaction. The study of CRAC channels has been complicated by the fact that they lose activity in the absence of extracellular Ca2+. Attempts to maintain current size by removing intracellular Mg2+ have been found to unmask Mg2+-inhibited cation (MIC/MagNuM/TRPM7) channels, which have been mistaken in several studies for the CRAC channel. Recent studies under conditions that prevent MIC activation reveal that CRAC channels use high-affinity binding of Ca2+ in the pore to achieve high Ca2+ selectivity but have a surprisingly low conductance for both Ca2+ (∼10fS) and Na+ (∼0.2 pS). Pore properties provide a unique fingerprint that provides a stringent test for potential CRAC channel genes and suggest models for the ion selectivity mechanism.

Original languageEnglish (US)
Pages (from-to)311-321
Number of pages11
JournalCell Calcium
Volume33
Issue number5-6
DOIs
StatePublished - 2003

Keywords

  • CRAC channel
  • CRAC current
  • Store-operated channels
  • T cells
  • TRP channels

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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