Regulation of voltage-gated calcium channels by the ER calcium sensor STIM1.

The endoplasmic reticulum (ER) Ca2+ sensor STIM1, best-known for its essential role in triggering influx of extracellular Ca2+ via Ca2+-release-activated channels when ER stores become depleted, unexpectedly also regulates Ca2+ entry through voltage-gated Ca2+ channels. In response to a drop in ER luminal Ca2+ level, this ER membrane-spanning sensor can contact voltage-gated Ca2+ channels in the plasma membrane and thereby inhibit Ca2+ influx through them. This previously unappreciated, interaction between ER Ca2+ level and magnitude of Ca2+ influx via voltage-gated Ca2+ channels may turn out to powerfully impact Ca2+ signaling in excitable cells, including neurotransmitter release, structural and functional postsynaptic plasticity, and transcription factor translocation.