1. How it works….step by step: At rest, the inside of the neuron is slightly negative due to a higher concentration of positively charged sodium ions outside the neuron.

2. When stimulated past threshold, sodium channels open and sodium rushes into the axon, causing a region of positive charge within the axon.

3. The region of positive charge causes nearby sodium channels to open. Just after the sodium channels close, the potassium channels open wide, and potassium exits the axon.

4. This process continues as a chain-reaction along the axon. The influx of sodium depolarizes the axon, and the overflow of potassium repolarizes the axon.

5. The sodium/potassium pump restores the resting concentrations of sodium and potassium ions

6. The Pump In Action

7. Action Potential

8. Na + / K + - ATPase

9. Na + / K + Facts The Na + -K + -ATPase is a highly-conserved integral membrane protein that is expressed in virtually all cells of higher organisms. As one measure of their importance, it has been estimated that roughly 25% of all cytoplasmic ATP is hydrolyzed by sodium pumps in resting humans. In nerve cells, approximately 70% of the ATP is consumed to fuel sodium pumps.

10. Physiologic and Pathologic Significance The ionic transport conducted by sodium pumps creates both an electrical and chemical gradient across the plasma membrane. This is critical not only for that cell but, in many cases, for directional fluid and electrolyte movement across epithelial sheets.

11. Some key examples include: The cell's resting membrane potential is a manifestation of the electrical gradient, and the gradient is the basis for excitability in nerve and muscle cells. Export of sodium from the cell provides the driving force for several facilitated transporters, which import glucose, amino acids and other nutrients into the cell. Translocation of sodium from one side of an epithelium to the other side creates an osmostic gradient that drives absorption of water. Important instances of this phenomenon can be found in the absorption of water from the lumen of the small intestine and in the kidney.absorption of water from the lumen of the small intestine

12. Depending on cell type, there are between 800,000 and 30 million pumps on the surface of cells. They may be distributed fairly evenly, or clustered in certain membrane domains, as in the basolateral membranes of polarized epithelial cells in the kidney and intestine.

13. Abnormalities in the number or function of Na + - K + -ATPases are thought to be involved in several pathologic states, particular heart disease and hypertension. Well-studied examples of this linkage include: Excessive renal reabsorption of sodium due to oversecretion of aldosterone has been associated with hypertension in humans. Several types of heart failure are associated with significant reductions in myocardial concentration of Na + -K + -ATPase.

14. Cation transport occurs in a cycle of changes triggered by phosphorylation of the pump. As currently understood, the sequence of events can be summarized as follows: The pump, with bound ATP, binds 3 intracellular Na + ions. ATP is hydrolyzed, leading to phosphorylation of a cytoplasmic loop of the pump and release of ADP. A conformational change in the pump exposes the Na + ions to the outside, where they are released. The pump binds 2 extracellular K + ions, leading to dephosphorylation. ATP binds and the pump reorients to release K + ions inside the cell. The pump is ready to go again.

15. Major hormonal controls over pump activity can be summarized as follows: Thyroid hormones appear to be a major player in maintaining steady-state concentrations of pumps in most tissues. This effect appears to result from stimulation of subunit gene transcription.Thyroid hormones Aldosterone is a steroid hormone with major effects on sodium homeostasis. It stimulates both rapid and sustained increases in pump numbers within several tissues. The sustained effect is due to enhanced transcription of the genes for both subunits.Aldosterone

16. CatecholaminesCatecholamines have varied effects, depending on the specific hormone and tissue. For example, dopamine inhibits Na + -K + -ATPase activity in kidney, while epinephrine stimulates pump activity in skeletal muscle. These effects seem to be mediated via phosphorylation or dephosphorylation of the pumps. InsulinInsulin is a major regulator of potassium homeostasis and has multiple effects on sodium pump activity. Within minutes of elevated insulin secretion, pumps have increased affinity for sodium and increased turnover rate. Sustained elevations in insulin causes upregulation. In skeletal muscle, insulin may also recruit pumps stored in the cytoplasm or activate latent pumps already present in the membrane.