The ubiquitous plasma membrane protein Na,K-ATPase (NKA) plays a fundamental role for the maintenance of cellular energy homeostasis. By exporting three Na+ ions and importing two K+ ions for each ATP hydrolyzed, NKA maintains the electrochemical gradients across the plasma membrane at the cost of 30% of body and 50% of brain energy consumption. In this talk some mechanisms by which NKA can act as a highly efficient regulator of energy consumption will be discussed.
Most of the presentation will deal with how NKA exerts control of its energy supplier, the mitochondria. NKA is also a signal transducer, which is activated by its specific ligands, the cardiotonic steroids (CTS). The CTS will, in non-saturating concentrations, initiate a signaling cascade that involves an oscillatory calcium signal that enters the mitochondria and acts to control mitochondrial integrity and the equilibrium between anti-apoptotic and apoptotic proteins. Examples of how NKA signaling protects against cell death because of malnutrition and exposure to high glucose will be presented.
Some of the mechanisms by which neurons have adapted to cope with the extraordinary demands to restore the perturbations in gradients following high neuronal activity in an energy efficient manner will also be briefly reviewed.