New Role of Sodium Pump

Abstract

The sodium pump is a plasma membrane protein, which is essential for maintaining the sodium and potassium ion gradient across the cell membrane. The pump consists of α and β subunits. The α2 subunit expresses tissue specifically, such as brain. We have developed mice that are defective of this gene and examined specific roles of α2 subunit. The homozygotes survived until birth, but they died immediately after birth due to the failure of respiration. We found that the lack of α2 subunit caused the imbalance of intracellular ion homeostasis critical for generation of the respiratory neuron activities in perinatal period. We propose a model for functional coupling between the α2 subunit and KCC2, the latter excludes Cl^- from the cytosol in respiratory center neurons. We also found that the α2 subunit plays a critical role in regulating neural activity in the developing amygdala and piriform cortex. Further supporting a role of the α2 subunit in the function of the amygdala, heterozygous adult mice showed augmented fear/anxiety behaviors and enhanced neuronal activity in the amygdala after conditioned fear stimuli. Interestingly, the adult heterozygotes developed obesity after middle age due to hyper-food intake in the light phase.