Sodium potassium pump

2. sodium-potassium pump

3. 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

4. Introduction
Transport through the cell membrane
1.Diffusion
2.Active transport

5.  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

6.  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

7. 2. Facilitated Diffusion:
Introduction

8.  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

9. 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

10. The Na+/K+-ATPase
The 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.

11.  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

12.  Structure:
tetramer 2β2α
sodium-potassium pump

13.  Function:
sodium-potassium pump

14.  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

15.  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

16.  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

17.  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

18.  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

19.  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

20.  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

21.  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