Metallomics and the Cell

Michael Jakob Voldsgaard Clausen, Hanne Poulsen, Clausen, Michael Jakob Voldsgaard, Poulsen, Hanne

Lucia Banci

All animals are characterized by steep gradients of Na(+) and K(+) across the plasma membrane, and in spite of their highly similar chemical properties, the ions can be distinguished by numerous channels and transporters. The gradients are generated by the Na(+),K(+)-ATPase, or sodium pump, which pumps out Na(+) and takes up K(+) at the expense of the chemical energy from ATP. Because the membrane is more permeable to K(+) than to Na(+), the uneven ion distribution causes a transmembrane voltage difference, and this membrane potential forms the basis for the action potential and for much of the neuronal signaling in general. The potential energy stored in the concentration gradients is also used to drive a large number of the secondary transporters responsible for transmembrane carriage of solutes ranging from sugars, amino acids, and neurotransmitters to inorganic ions such as chloride, inorganic phosphate, and bicarbonate. Furthermore, Na(+) and K(+) themselves are important enzymatic cofactors that typically lower the energy barrier of substrate binding.In this chapter, we describe the roles of Na(+) and K(+) in the animal cell with emphasis on the creation and usage of the steep gradients across the membrane. More than 50 years of Na(+),K(+)-ATPase research has revealed many details of the molecular machinery and offered insights into how the pump is regulated by post-translational modifications and specific drugs.