Open and shut: pain signals in nerve cells

Our daily function depends on signals traveling between nerve cells (neurons) along fine-tuned pathways. Central nervous system neurons contain acid-sensing ion channel 1a (ASIC1a), a protein important in sensing pain and forming memories of fear. An ion channel lodged in the cell membrane that provides a pathway for sodium ions to enter the cell, ASIC1a opens and closes in response to changes in extracellular proton concentrations. When protons accumulate outside the neuron, the channel opens, allowing sodium ions to flow into the cell, depolarizing the cell membrane and generating an electrical signal. The channel eventually becomes desensitized to protons and the gate closes. Scientists have visualized both the open and desensitized channel structures, but the third structure, which forms when the protons dissipate and the channel closes, remained elusive. Using protein crystallography at the ALS, researchers finally visualized the closed channel.

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Animation: As the proton concentration increases or decreases, the gated channel ASIC1a toggles between open and closed positions, controlling the timing of signals traveling through the cell membrane of one neuron en route to the next.