Sigma-1 receptors: a new pathway for the modulation of store-operated calcium entry

SOCE (store-operated Ca²⁺ entry) is a ubiquitous mechanism for Ca²⁺ influx in animal cells. In a recent issue of the Biochemical Journal, Brailoiu and colleagues reported that cocaine attenuates SOCE in rat brain microvascular endothelial cells, via a mechanism that requires the expression and activation of the sigma-1 receptor, a chaperone located in the endoplasmic reticulum–mitochondrion interface that modulates intracellular Ca²⁺ homoeostasis and cell survival. This study envisages a pathway through which cocaine modulates endothelial function via regulation of SOCE. The regulation of SOCE by sigma-1 receptors provides a novel and important pathway in Ca²⁺ signalling.