The concentration of K+ is typically 10–30 times higher inside cells than outside, whereas the reverse is true of Na+ (see Table 11–1, p. 598). A Na+-K+ pump, or Na+K+ ATPase, found in the plasma membrane of virtually all animal cells maintains
Figure 11–13 The structure of the sarcoplasmic reticulum Ca2+ pump. The ribbon model (left), derived from x-ray crystallographic analyses, shows the pump in its phosphorylated, ATP-bound state. The three globular cytosolic domains of the pump—the nucleotide-binding domain (dark green), the activator domain (blue), and the phosphorylation domain (red), also shown schematically on the right—change conformation dramatically during the pumping cycle. These changes in turn alter the arrangement of the transmembrane helices, which allows the Ca2+ to be released from its binding cavity into the SR lumen (Movie 11.3). (PDB code: 3B9B.) these concentration differences. Like the Ca2+ pump, the Na+-K+ pump belongs to the family of P-type ATPases and operates as an ATP-driven antiporter, actively pumping Na+ out of the cell against its steep electrochemical gradient and pumping K+ in (Figure 11–15).
We mentioned earlier that the Na+ gradient produced by the Na+-K+ pump drives the transport of most nutrients into animal cells and also has a crucial role in regulating cytosolic pH. A typical animal cell devotes almost one-third of its energy to fueling this pump, and the pump consumes even more energy in nerve cells and in cells that are dedicated to transport processes, such as those forming kidney tubules.
Since the Na+-K+ pump drives three positively charged ions out of the cell for every two it pumps in, it is electrogenic: it drives a net electric current across the membrane, tending to create an electrical potential, with the cell’s inside being negative relative to the outside. This electrogenic effect of the pump, however, seldom directly contributes more than 10% to the membrane potential. The remaining 90%, as we discuss later, depends only indirectly on the Na+-K+ pump.
Figure 11–14 The pumping cycle of the sarcoplasmic reticulum Ca2+ pump.
Ion pumping proceeds by a series of stepwise conformational changes in which movements of the pump’s three cytosolic domains [the nucleotide-binding domain (N), the phosphorylation domain (P), and the activator domain (A)] are mechanically coupled to movements of the transmembrane α helices. Helix movement opens and closes passageways through which Ca2+ enters from the cytosol and binds to the two centrally located Ca2+ binding sites. The two Ca2+ then exit into the SR lumen and are replaced by two H+, which are transported in the opposite direction. The Ca2+-dependent phosphorylation and H+-dependent dephosphorylation of aspartic acid are universally conserved steps in the reaction cycle of all P-type pumps: they cause the conformational transitions to occur in an orderly manner, enabling the proteins to do useful work. (Adapted from C. Toyoshima et al., Nature 432:361–368, 2004 and
J.V. Møller et al., Q. Rev. Biophys. 43:501– 566, 2010.)
Figure 11–15 The function of the Na+-K+ pump. This P-type ATPase  actively pumps Na+ out of and K+ into a cell against their electrochemical gradients. It is structurally closely related to the  Ca2+ ATPase but differs in its selectivity for ions: for every molecule of ATP hydrolyzed by the pump, three Na+ are pumped out and two K+ are pumped in. As in the  Ca2+ pump, an aspartate is phosphorylated and dephosphorylated during the pumping cycle (Movie 11.4).