Regulation of Na+/K+-ATPase Activity in the Nervous System

Abstract

The Na+/K+-ATPase or sodium pump (NKA) is a membrane-anchored protein responsible for creating and maintaining the Na+ and K+ gradients across the plasma membrane of animal cells by using ATP hydrolysis to move three Na+ out of the cell and two K+ into the cell. In the nervous system, NKA activity is essential for the proper functioning of neurons and glial cells and for the driving of diverse brain processes. Regulation of NKA activity in the brain is achieved through multitude of complex mechanisms. The purpose of this chapter is to present an overview of mechanisms through which neurotransmitters such as glutamate, dopamine, and serotonin regulate NKA activity in neurons and glial cells. Here, the focus is on the signaling pathways and protein kinases that mediate neurotransmitter effects on the NKA activity. In addition, the chapter considers the regulation of neuronal and glial NKA activity by its direct interacting partners, that is, a diverse plasma membrane, synapse associated, cytoskeleton, and signaling cytoplasmic proteins that form complexes with NKA in the brain. Such complexes not only regulate NKA activity but also enable the pump to function as a signal transducer in the brain. In view of important physiological role that NKA plays in the brain, the perturbed regulation of NKA activity in neurons and glial cells and its association with the onset and progress of nervous system disorders is also addressed.