The electrogenicity of the Na⁺/K⁺-ATPase poses challenges for computation in highly active spiking cells

Summary

The evolution of the Na⁺/K⁺-ATPase laid the foundation for ion homeostasis and electrical signalling. While not required for restoration of ionic gradients, the electrogenicity of the pump (resulting from its 3:2 stoichiometry) is useful to prevent runaway activity. As we show here, electrogenicity could also come with disadvantageous side effects: (1) an activity-dependent shift in a cell’s baseline firing and (2) interference with computation, disturbing network entrainment when inputs change strongly. We exemplify these generic effects in a mathematical model of the weakly electric fish electrocyte, which spikes at hundreds of Hz and is exposed to abrupt rate changes when producing behaviorally-relevant communication signals. We discuss biophysical strategies that may allow cells to mitigate the consequences of electrogenicity at additional metabolic cost and postulate an interesting role for a voltage-dependence of the Na⁺/K⁺-ATPase. Our work shows that the pump’s electrogenicity can open an additional axis of vulnerability that may play a role in brain disease.