Introduction

Abstract

More than two decades have elapsed since the discovery of capacitative Ca²⁺ entry, also known as store-operated Ca²⁺ entry (SOCE), by J.W. Putney, Jr. in 1986. SOCE was first reported as a mechanism for receptor-regulated Ca²⁺ influx controlled by inositol 1,4,5-trisphosphate that allows refilling of the intracellular Ca²⁺ compartments once agonist stimulation has finished. In fact, the term “capacitative” calcium entry was originally meant to describe the cyclic loading and discharge of a Ca²⁺ store, similar to an electrical circuit, where charging of a capacitor is associated with flow of a capacitative current. The initial hypothesis, which limited the role of SOCE to the refilling of the intracellular Ca²⁺ pools after or during agonist stimulation, was soon modified by the same research group providing evidence to the idea that store refilling did not involve a direct Ca²⁺-route into the endoplasmic reticulum, but rather resulted from a sequential Ca²⁺ entry into the cytoplasm and subsequent accumulation in the Ca²⁺ stores by SERCA pumps. This new concept of SOCE significantly broadened the functional implications of SOCE in Ca²⁺ signaling as this mechanism serves as a Ca²⁺ source for agonist-stimulated Ca²⁺ mobilization (Putney 2007).