Store-operated ion channels: A growing family ?

The depletion of the endoplasmic reticulum (ER) Ca 2+ stores is known to activate a Ca 2+ route of the plasma membrane known as store-operated Ca 2+ entry (SOCE). Stromal interaction molecules (STIM1-2) and Orai1-3 proteins are regarded as the central molecular core components of SOCE. In a recent article, Patel and colleagues have identified a new type of coupling linking the Ca 2+ status of the ER and the activity of pannexin 1 (Panx1) ion channels distinct from Orai. This work further illustrates that Orai channels are far from being the exclusive partners of STIM proteins since these ER Ca 2+ sensors interact with a large diversity of targets and control several biological responses independently of Orai channels. Patel et al present an exciting new perspective on the contribution of the ER Ca 2+ release that recruits distinct types of cell surface ion channels such as Ca 2+ -selective (Orai) and nonselective (Panx1) channels. This study provides new insight into the complexity of store-operated ion channels signalling. Future studies will be required to better understand the contribution of this neuronal store-operated Panx1 response in neuronal pathophysiology.