ATP from subplasmalemmal mitochondria controls Ca2+-dependent inactivation of CRAC channels

Abstract

A sustained Ca2+ entry is the primary signal for T lymphocyte activation after antigen recognition. This Ca2+ entry mainly occurs through store-operated Ca2+ channels responsible for a highly selective Ca2+ current known as ICRAC. Ca2+ ions act as negative feedback regulators of ICRAC, promoting its inactivation. Mitochondria, which act as intracellular Ca2+ buffers, have been proposed to control all stages of CRAC current and, hence, intracellular Ca2+ signaling in several types of non-excitable cells. Using the whole-cell configuration of the patch clamp technique, which allows control of the intracellular environment, we report here that respiring mitochondria located close to CRAC channels can regulate slow Ca 2+-dependent inactivation of ICRAC by increasing the Ca2+-buffering capacity beneath the plasma membrane, mainly through the release of ATP. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.