TPC1 vacuole SV channel gains further shape - voltage priming of calcium-dependent gating.

Across phyla, voltage-gated ion channels (VGICs) allow excitability. The vacuolar two-pore channel AtTPC1 from the tiny mustard plant Arabidopsis thaliana has emerged as a paradigm for deciphering the role of voltage and calcium signals in membrane excitation. Among the numerous experimentally determined structures of VGICs, AtTPC1 was the first to be revealed in a closed and resting state, fueling speculation about structural rearrangements during channel activation. Two independent reports on the structure of a partially opened AtTPC1 channel protein have led to working models that offer promising insights into the molecular switches associated with the gating process. We review new structure-function models and also discuss the evolutionary impact of two-pore channels (TPCs) on K homeostasis and vacuolar excitability.