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In eukaryotic cells, hormones and neurotransmitters that engage the phosphoinositide pathway evoke a biphasic increase in intracellular free Ca(2+) concentration: an initial transient release of Ca(2+) from intracellular stores is followed by a sustained phase of Ca(2+) influx. This influx is generally store dependent. Most attention has focused on the link between the endoplasmic reticulum and store-operated Ca(2+) channels in the plasma membrane. Here, we describe that respiring mitochondria are also essential for the activation of macroscopic store-operated Ca(2+) currents under physiological conditions of weak intracellular Ca(2+) buffering. We further show that Ca(2+)-dependent slow inactivation of Ca(2+) influx, a widespread but poorly understood phenomenon, is regulated by mitochondrial buffering of cytosolic Ca(2+). Thus, by enabling macroscopic store-operated Ca(2+) current to activate, and then by controlling its extent and duration, mitochondria play a crucial role in all stages of store-operated Ca(2+) influx. Store-operated Ca(2+) entry reflects a dynamic interplay between endoplasmic reticulum, mitochondria and plasma membrane.

Original publication

DOI

10.1093/emboj/19.23.6401

Type

Journal article

Journal

EMBO J

Publication Date

01/12/2000

Volume

19

Pages

6401 - 6407

Keywords

Animals, Anti-Bacterial Agents, Antimycin A, Calcium, Calcium Channels, Calcium-Transporting ATPases, Cell Membrane, Coloring Agents, Cytosol, Electrophysiology, Endoplasmic Reticulum, Mitochondria, Models, Biological, Oxygen Consumption, Patch-Clamp Techniques, Rats, Ruthenium Red, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Time Factors, Tumor Cells, Cultured