ATP1A2. We have previously written about ATP1A3, one of the neuronal ATPases, which, together with ATP1A2, actively works to maintain the electrochemical gradient across cell membranes. In our previous post, we likened ATP1A3 to Sisyphus, who was punished by the gods to spend eternity exerting his strength to push a boulder up a hill, only for the boulder to roll back down, over and over again. Similarly, the ATPases utilize energy (ATP) to transport Na+ out of the cell and K+ into the cell, even while other voltage-gated channels effortlessly open to allow Na+ and K+ to move in the opposite direction, forcing the boulder back down the hill. However, from another perspective we can see that far from being Sisyphus, the ATPases are the noblest of facilitators, proudly maintaining the membrane electrochemical gradient in order to enable all other cell processes to function. If you will allow me further anthropomorphization of submicroscopic proteins – far from being inconsiderate to the task of the ATPases, our voltage-gated Na+, K+, and Ca++ channels are reliant on these stoic transporters to get their jobs done. It is because of the electrochemical gradient that cells are able to propagate action potentials down an axon, signal axon terminals to release neurotransmitters, and continue to send electrochemical signals on to subsequent cells. Both ATP1A2 and ATP1A3 code for subunits of the Na+-K+ ATPase, where ATP1A2 codes for the α2 subunit and ATP1A3 for the α3 subunit. Both ATP1A3 and ATP1A2 are expressed in neurons during embryonal brain development, and while ATP1A3 remains neuronal postnatally, ATP1A2 is relegated to the glial cells postnatally and into adulthood. In addition to their role in active ion transport, Na+-K+ ATPases are thought to play a part in regulating signaling pathways and gene transcription. Given its localization to astrocytes, which act as a so-called “glutamate sink” to prevent glutamate excitotoxicity within the synapse, ATP1A2 is thought to be critical for the process of glutamate clearance and prevention of excitotoxicity (Du et al 2020). 

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