Electrical signals in the ER are cell type and stimulus specific with extreme spatial compartmentalization in neurons.

The endoplasmic reticulum (ER) is a tortuous organelle that spans throughout a cell with a continuous membrane containing ion channels, pumps, and transporters. It is unclear if stimuli that gate ER ion channels trigger substantial membrane potential fluctuations and if those fluctuations spread beyond their site of origin. Here, we visualize ER membrane potential dynamics in HEK cells and cultured rat hippocampal neurons by targeting a genetically encoded voltage indicator specifically to the ER membrane.