Key Area 3
(b) Ion transport pumps and generation of ion gradients
The importance of ion transport
Understanding how molecules move across membranes and how ion gradients are established, maintained and controlled forms the basis of fundamental research in many prominent research institutes across the UK, including the University of Dundee's School of Life Sciences.
Within the area of Computational Biophysics and Drug Discovery, researchers are devoted to understanding how "cardiac ion channels function to control heartbeat - and how their malfunction can lead to arrhythmia and sudden death". They use their insights to design anti-arrhythmic drugs.
For a solute carrying a net charge, e.g. sodium ions, the concentration gradient and the electrical potential difference combine to form the electrochemical gradient that determines the transport of the solute.
In the diagram opposite, you can see the phospholipid bilayer dividing the intra- and extracellular space. There are uneven distributions of ions (carrying positive or negative charges) on either side of the membrane. The large triangles indicate the direction of ion movement.
However, it should be clear that a distribution in their relative concentrations is not the only consequence here; there is a charge discrepancy across the membrane. This is referred to as the "membrane potential".
Membrane potential
A membrane potential (an electrical potential difference) is created when there is a difference in electrical change on the two sides of the membrane.
In neurons, the membrane potential is typically between -60 and -80mV when the cell is not transmitting signals.
In the diagram opposite, the electrode is measuring the membrane potential across the membrane. The "fluid outside the cell" must have more positive ions relative to the "cytoplasm" as the reading is -80mV; the minus sign means that the inside of the cell is negative relative to the outside.
Ion pumps use energy from the hydrolysis of ATP to establish and maintain these ion gradients. It's time to meet a very important player in maintaining ion gradients (including the resting membrane of neurons): The Sodium-Potassium pump.
Task 51
Sketch the axon of a neuron, showing the resting membrane potential recorded using an electrode.
The Sodium-Potassium (Na/K) Pump
The Na/K-pump, also known as the Na/K-ATPase, is a vital transmembrane ion transporter protein found in animal cells. It transports ions against a steep concentration gradient using energy directly from ATP hydrolysis. It actively transports sodium ions out of the cell and potassium ions into the cell.
It is so important that a lot of our metabolic energy is devoted to its operation.
It is found in most animal cells and accounts for a high proportion (~25%) of the basal metabolic rate of many organisms.
It has many important roles
In epithelial cells of the small intestine, the sodium-potassium pump generates a sodium ion gradient across the plasma membrane. This sodium gradient drives the active transport of glucose via the glucose symport transporter we met in KA3a: glucose symport involves the co-transport of sodium ions into cells (down its concentration gradient) and glucose (against its concentration gradient) at the same time and in the same direction - more explanation below!
Glucose symport and Na/K pump
Let's look at this more closely.
The Na/K pump (green, 1): In this diagram, the Na/K pump uses ATP hydrolysis to actively transport sodium ions into the blood stream. This is important because it creates a low sodium concentration in the cytosol of epithelial cells lining the intestine.
Glucose symporter (blue, 2): Because of the low sodium concentration inside epithelial cells (due to the Na/K pump), sodium within the intestinal lumen can move DOWN its concentration gradient into the epithelial cells. The movement of sodium is coupled to the active transport of glucose from the intestinal lumen into the epithelial cells.
Glucose transporter (orange, 3): Glucose is removed from the epithelial cell cytosol into the bloodstream via a GLUT transport protein.
Task 52
Reflect back on your own notes about glucose symport from task 50 in Key Area 3a. Can you add anything else in now to support your understanding of this membrane transport protein?
Task 53
"The Na/K pump plays a critical role in the absorption of glucose from the small intestine". Do you agree or disagree with this statement? Explain your answer.
How does the pump work?
- Sodium ions bind
At the start of the cycle, the pump has a high affinity for sodium ions inside the cell. 3 sodium ions binds to the pump. This is due to its particular (dephosphorylated) conformation at this stage of the cycle.
2. Pump Phosphorylation
The pump is then phosphorylated by ATP hydrolysis and, as a consequence, undergoes a conformational change.
3. Conformational change
The pump now has a more open conformation towards the extracellular space and a lower affinity for sodium ions. The pump releases the 3 bound sodium ions to the extracellular space.
4. Potassium binds
In this phosphorylated state, the pump has high affinity for potassium ions; 2 potassium binds from the extracellular space bind to the pump.
5. Pump dephosphorylation
The pump then undergoes dephosphorylation. Dephosphorylation triggers a second conformation change.
6. Conformational change
In this new conformation, the pump is open to the intracellular space and has a lowered affinity for potassium ions, which are now released inside the cell. The pump now has a high affinity for sodium ions, which rebind from the intracellular environment. And the cycle begins again!
End result...
For each ATP hydrolysed, 3 sodium (positive) ions are transported out of the cell and 2 potassium (positive) ions are transported into the cell. This establishes both concentration gradients and an electrical gradient.
Therefore, the intracellular environment is negative relative to the outside, resulting in a resting membrane potential of approximately -70mV.
Task 54
In your notes, include a step-by-step flowchart to illustrate the mechanism of the Na/K pump.
Suggested answers are here.
Now go to SCHOLAR "3.2 Ion transport pumps and generation of ion gradients" for consolidation.
To complete this Key Area, you should also look at:
3.3 Learning Points
3.4 Extended response question
3.5 End of topic test
Retrieval practice - Memory platform
Answer the following questions to try and link your knowledge from the past few areas:
How would you define the Na/K-pump in terms of it being a "membrane protein"? (peripheral/integral/transmembrane/channel/transporter?)
Considering your response to question 1, can you predict the types of amino acids you might expect to find in different regions of the protein? Explain your prediction.
Reflect on the role of the Na/K-pump in maintaining the resting membrane potential of a neuron. During an action potential, this membrane potential must change. Can you make a prediction about how this might happen by reflecting on what you have learned during Key Area 3a.
Suggested responses are available here.
Click here for a Quizlet on Topic 1, Key Area 3b
Time to create your own content for our online class blog and become a published author! Write a piece that showcases your learning of Key Area 3 on Membrane Proteins.
Your teacher might now issue you with Learner Check 10 to check your learning of Topic 1 (Key Area 2 and 3) so far.
