title: 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 I(CRAC). Ca2+ ions act as negative feedback regulators of I(CRAC), 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 Ca2+-dependent inactivation of I(CRAC) by increasing the Ca2+-buffering capacity beneath the plasma membrane, mainly through the release of ATP.
authors.affiliation: Department of Toxicology and Pharmacology, Instituto de Farmacología y Toxicología, Facultad de Veterinaria, Universidad Complutense de Madrid, Avenida Puerta de Hierro, s/n. 28040 Madrid, Spain.
authors.forename: Gema B
authors.initials: GB
authors.lastname: Montalvo
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Artalejo
authors.forename: Juan A
authors.initials: JA
authors.lastname: Gilabert
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004594:Electrophysiology; D005434:Flow Cytometry; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism*; D000071740:ORAI1 Protein; D018408:Patch-Clamp Techniques; D015398:Signal Transduction
chemical_list: D015220:Calcium Channels; D002614:Chelating Agents; D008565:Membrane Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000255:Adenosine Triphosphate; D002118:Calcium