The sodium-potassium pump, also known as the Na+-K+ ATPase pump, transports sodium and potassium ions across cell membranes. It pumps 3 sodium ions out of the cell in exchange for 2 potassium ions into the cell, maintaining ion gradients crucial for nerve and muscle function. First discovered in 1957, it is critical for establishing the resting membrane potential and driving secondary active transport of nutrients into cells.
2. Introduction
➢Sodium-Potassium Pump or Na+ -K+ -ATPase is an integral
membrane protein found in the cells of all higher eukaryotes.
➢It is responsible for translocating sodium and potassium ions
across the cell membrane utilizing ATP as the driving force
3. Introduction
➢For every three sodium ions pumped out of the cell, two potassium ions
are pumped in.
➢This transport produces both a chemical and an electrical gradient across
the cell membrane.
➢The electrical gradient is essential for maintaining the resting potential of
cells and for the excitable activity of muscle and nerve tissue.
➢The sodium gradient is used to drive numerous transport processes,
including the translocation of glucose, amino acids, and other nutrients
into cells.
4. Introduction
➢Physiologically, Na+ - K + ATPase present in organs such as the intestines
and the kidney regulates fluid reabsorption and electrolyte movement by
establishing an ionic gradient across epithelial membranes.
➢It is estimated that approximately 23% of the ATP consumed in humans at
rest is utilized by the sodium pump.
➢The Na+--K+ -ATPase is a member of the P-type class of active cation
transport proteins of ATPases
5. History
➢The sodium-potassium pump was
discovered in 1957 by the Danish scientist
Jens Christian Skou.
➢He was awarded a Nobel Prize for his work
in 1997.
6. Structure
➢The Na+ - K + -ATPase can
function as an α β dimer.
➢There are four isoforms of α(1-
4) and three isoforms of β
expressed in a tissue-specific
fashion.
7. Structure
➢The α subunit contains the ATP binding site, the phosphorylation site, and
amino acids essential for the binding of cations and cardiac glycosides.
➢This subunit plays a major role in the catalytic function of the enzyme.
➢The β subunit appears to be involved in maturation of the enzyme,
localization of the ATPase to the plasma membrane, and stabilization of a K
+ -bound intermediate form of the protein.
8. Electrogenic pump
➢Drives 3 positively charged ions (Na+ ) out of the cell for every 2 it pumps
in (K+ ).
➢It drives a net electrical charge across the membrane ,tending to create an
electrical potential, with cell’s inside being negative relative to outside.
➢This electrogenic effect of the pump, how ever seldom directly contributes
more than 10% of the membrane potential.
9. Forms of sodium - potassium pump
➢Na+ - K + ATPase exists in two forms-
➢E1 Form: E1 has an inward –facing high affinity Na+ binding site and reacts
with ATP to form the activated product E1~P only when Na+ is bound.
➢E2 form : E2 –P has an outward –facing high affinity K+ binding site and
hydrolyses to form Pi + E2, only when K+ is bound .
10. Mechanism
The (Na+ -K + )-ATPase operates in
accordance with the following ordered
sequential reaction scheme:
1)E1: 3Na+ ,which acquired its Na+ inside
the cell, binds ATP to yield the tertiary
complex E1 .ATP.Na+
2)The tertiary complex reacts to form the
high energy aspartyl phosphate
intermediate E1~P.3Na+
3)This high energy intermediate relaxes to
its low energy conformation ,E2 -P.3Na+ and
relaxes its bound sodium outside the cell
11. 4)E2 -P binds 2K+ from outside
the cell to form E2 -P.2k+ .
5) The phosphate group is
hydrolyzed, yielding E2 .2K+
6) E2 .2K+ changes
conformation, releases its 2K+
inside the cell ,and replaces its
Na+ , thereby completing the
transport cycle.
12. INHIBITION
➢The pump requires binding by Na+ , K+ and ATP for its operation. Therefore
, if the concentration of any of these substances is too low , the pump does
not function.
➢When the temperature is reduced.
➢During oxygen lack.
➢Metabolic Poisons e.g. 2,4 DNP that prevents the formation of ATP.
13. Function
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 mechanism moves 3 sodium ions out and
moves 2 potassium ions in.
➢Thus, in total removing one positive charge carrier from the intracellular
space
14. Function
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.
15. Function
Controlling Cell Volume
➢Failure of the Na+ -K +pumps can result in swelling of the cell.
➢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.
16. Function
Controlling Neuron activity.
➢The Na+ -K + pump has been shown to control and set the intrinsic activity
mode of cerebellar Purkinje neurons, accessory olfactory bulb mitral cells
and probably other neuron types.
➢ Pump not simply be a homeostatic molecule for ionic gradients; but could
be a computation element in the cerebellum and the brain .
➢Mutation in the Na+ -K + pump causes rapid onset dystonia parkinsonism.