Neurons in the brain require a continuous supply of oxygen for normal activity. If the level of oxygen in the brain decreases—for example when a blood vessel becomes blocked—neurons begin to die, and permanent brain damage can result. A shortage of oxygen first causes sodium ion channels within the surface membrane of the neurons to open. Sodium ions then flow into the cells through these open channels to trigger a cascade of events inside the cells that ultimately results in their death.
In “SUMOylation of NaV1.2 channels mediates the early response to acute hypoxia in central neurons” (Elife), Plant et al. now reveal how oxygen deficiency, otherwise known as hypoxia, rapidly increases the flow of sodium ions into brain cells. By inducing hypoxia in neurons from rat brain, Plant et al. show that a lack of oxygen causes SUMOylation, a process whereby a series of enzymes work together to attach a Small Ubiquitin-like Modifier (or SUMO) protein, of specific sodium ion channels in under a minute. The channels linked to the SUMO protein, a subtype called Nav1.2, open more readily than unmodified channels, allowing more sodium ions to enter the neurons.
Plant et al. study granule cells of the cerebellum, the most numerous type of neuron in the human brain. Further investigation is required to determine if SUMOylation of Nav1.2 channels underlies the response of other neurons to hypoxia as well. It also remains to be discovered whether molecules that block the SUMOylation of Nav1.2 channels, or that prevent the flow of sodium ions through these channels, could reduce the number of brain cells that die in low-oxygen conditions such as stroke.