Most of the proteins listed above mediate transport by an antiport mechanism, exchanging alkali metal cations for protons. Therefore, a proton motive force across membranes serves as a source of energy to pump alkali metal cations against their gradients. Nevertheless, in some cases (e.g., sudden alkalinization of cytosol at high pHout), cells can use the outward gradient of potassium across the plasma membrane as a driving force to transport protons against their gradient into the cells . Under normal physiological conditions, the secondary active antiporters localized in the plasma and organellar membranes depend on the activity of primary active transporters that build up the necessary gradient of protons. In yeast cells, this function is fulfilled by the plasma membrane and vacuolar ATPases.