sodium-potassium pump

Introduction

The Lipid Barrier of the Cell Membrane:

The lipid bilayer is not miscible with either the extracellular fluid or the intracellular fluid. Therefore, it

constitutes a barrier against movement of water molecules and water-soluble substances between the

extracellular and intracellular fluid compartments. However few substances can penetrate this lipid bilayer,

diffusing directly through the lipid substance itself; this is true mainly of lipid-soluble substances

Introduction

Transport through the cell membrane

1.Diffusion

2.Active transport

Diffusion:

1. simple diffusion:

Simple diffusion can occur through the cell membrane by two pathways: (1) through the interstices of the lipid bilayer if the diffusing substance is lipid soluble and (2) through watery channels that penetrate all the way through some of the large transport proteins

Introduction

The protein channels are distinguished by two important characteristics:

They are often selectively permeable to certain substances

many of the channels can be opened or closed by gates

Introduction

2. Facilitated Diffusion:

Introduction

Active transport:

1.Primary Active Transport:

In primary active transport, the energy is derived directly from breakdown of adenosine triphosphate (ATP) or of some other high-energy phosphate compound.

Introduction

2. Secondary Active Transport—Co-Transport and Counter-Transport:

In secondary active transport, the energy is derived secondarily from energy that has been stored in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane, created originally by primary active transport

Introduction

The Na+/K+-ATPaseThe Na+/K+-ATPase pumps sodium out of cells, while pumping potassium into cells. It has antiporter-like activity but is not actually an antiporter since both molecules are moving against their concentration gradient.

Discovery:Na+/K+ -ATPase was discovered by Jens Christian Skou in 1957 while working as assistant professor at the Department of Physiology, University of Aarhus, Denmark.In 1997, he received one-half of the Nobel Prize in Chemistry "for the first discovery of an ion-transporting enzyme, Na+/K+ -ATPase.

sodium-potassium pump

Structure:

tetramer 2 2  β α

sodium-potassium pump

Function:

sodium-potassium pump

Resting potential

Transport

Controlling cell volume

Controlling neuron activity states

Resting potential:

In order to maintain the cell membrane potential, cells keep a low concentration of sodium ions and high levels of potassium ions within the cell (intracellular). The sodium-potassium pump moves 3 sodium ions out and moves 2 potassium ions in, thus, in total, removing one positive charge carrier from the intracellular space.

sodium-potassium pump

Transport:

Export of sodium from the cell provides the driving force for several secondary active transporters membrane transport proteins, which import glucose, amino acids, and other nutrients into the cell by use of the sodium gradient.

sodium-potassium pump

Controlling cell volume

A cell's osmolarity is the sum of the concentrations of the various ion species and many proteins and other organic compounds inside the cell. When this is higher than the osmolarity outside of the cell, water flows into the cell through osmosis. This can cause the cell to swell up and lyse. The Na+-K+ pump helps to maintain the right concentrations of ions. Furthermore, when the cell begins to swell, this automatically activates the Na+-K+ pump.

sodium-potassium pump

Controlling neuron activity states

The Na+-K+ pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons.This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computation element in the cerebellum and the brain. Indeed, a mutation in the Na+-K+ pump causes rapid onset dystonia parkinsonism, which has symptoms to indicate that it is a pathology of cerebellar computation

sodium-potassium pump

Mechanism: 1. The pump, after binding ATP, binds 3 intracellular Na+ ions.

2. ATP is hydrolyzed, leading to phosphorylation of the pump at a highly conserved aspartate residue and subsequent release of ADP.

3. A conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of the pump has a low affinity for Na+ ions, so they are released.

4. The pump binds 2 extracellular K+ ions. This causes the dephosphorylation of the ump, reverting it to its previous conformational state, transporting the K+ ions into the cell.

5. The unphosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound K+ ions are released. ATP binds, and the process starts again

sodium-potassium pump

Regulation:

1.Endogenous

The Na+/K+-ATPase is upregulated by cAMP.Thus, substances causing an increase in cAMP upregulate the Na+/K+-ATPase. These include the ligands of the Gs-coupled GPCRs. In contrast, substances causing a decrease in cAMP downregulate the Na+/K+-ATPase. These include the ligands of the Gi-coupled GPCRs.

sodium-potassium pump

Exogenous

The Na+-K+-ATPase can be pharmacologically modified by administrating drugs exogenously.

For instance, Na+-K+-ATPase found in the membrane of heart cells is an important target of cardiac glycosides (for example digoxin and ouabain), inotropic drugs used to improve heart performance by increasing its force of contraction.

sodium-potassium pump

References: Hall, John E., and Arthur C. Guyton. Textbook of medical physiology. St. Louis, Mo: Elsevier Saunders. ISBN

0-7216-0240-1, 2006.

Giannatselis, H., Calder, M., & Watson, A. J. (2011). Ouabain stimulates a Na+/K+-ATPase-mediated SFK-activated signalling pathway that regulates tight junction function in the mouse blastocyst. PloS one, 6(8), e23704.

Forrest, M. D., Wall, M. J., Press, D. A., & Feng, J. (2012). The sodium-potassium pump controls the intrinsic firing of the cerebellar Purkinje neuron.PloS one, 7(12), e51169..

Fremont, R., & Khodakhah, K. (2012). Alternative approaches to modeling hereditary dystonias. Neurotherapeutics, 9(2), 315-322.

Burnier, M. (Ed.). (2007). Sodium in health and disease. CRC Press.

sodium-potassium pump