04-11-21 - Ionic Basis of Action Potential Flashcards
Learning Outcomes
- Define Na+ and K+ equilibrium potential, depolarisation, repolarisation and hyperpolarisation
- Compare the response of electrically excitable and inexcitable cells to depolarisation
- Describe the main characteristics of an action potential
- Describe the relationship between the changes in membrane permeability and membrane voltage
- Explain the role of voltage-gated and time-dependent Na and K channels in the action potential
What are the concentration gradients of Sodium and Potassium inside and outside of the cell?
What is membrane potential?
What is it measured in?
Which way do ions move?
What drives membrane potential?
How is it brought about?
Why might some cells have different resting potential?
- Na+ outside – 140mM (millimolar), Na inside – 15mM
- K+ outside – 5mM, K+ inside 140mM
- Membrane potential is the voltage difference between the inner and outer surface of the cell (charge inside of the cell with respects to outside of the cell - measured in millivolts – mV)
- Positive ions are attracted to the negative side
- Negative ions are attracted to the positive side
- membrane potential is driven by the Na+/K+ ATPase
- Membrane potential is brought about by this asymmetry in the concentrations of cations (Na+ and K+)
- Some cells may have different resting potential due to different concentrations of ions
What are the 5 steps which describe how the potassium equilibrium potential forms?
Is this potential positive or negative? What is the value for potassium’s equilibrium potential?
1) Potassium wants to flow down its concentration gradient and move out of the cell via membrane proteins, such as transporters or ion channels
2) This will result in the generation of a negative membrane potential, as potassium is a positively charged ion (inside of cell more negative than outside)
3) This negative charge will also draw positively charged potassium back into the cell
4) The efflux of potassium is caused by a concentration gradient, whereas the influx of potassium is driven by an electrical gradient
5) When this influx and efflux balance, the potential we measure at this point is known as the potassium equilibrium potential
- This is a negative potential, as potassium flows down its concentration gradient by going out of the cell, which will create a negative membrane potential
- Potassium’s equilibrium potential is -105mV
What are the 5 steps which describe how the sodium equilibrium potential forms?
Is this potential positive or negative?
What is the value for sodium’s equilibrium potential?
1) Sodium wants to flow down its concentration gradient into the cell via transporters or ion channels
2) This will generate appositive membrane potential, as sodium is a positive ion
3) This positive charge will draw sodium back out of the cell
4) The efflux of sodium is driven by an electric potential, whereas the influx of sodium is driven by a concentration gradient
5) When this influx and efflux balance, the potential we measure at this point is known as the sodium equilibrium potential
- This is a positive potential, as the sodium will flow down the concentration gradient into the cell
- Sodium’s equilibrium potential is 65mV
What are the 3 steps to generating the resting membrane potential?
Why is the resting potential not the same as the potassium equilibrium potential?
How does permeability of the membrane in sodium and potassium differ?
1) Potassium flows down its concentration outside of the cell via potassium transporters and ion channels
2) Because K+ ions are not accompanied by anions (negatively charged ions) charge separation occurs, and the electrical potential in the cell’s interior becomes negative with respect to the outside of the cell
3) This negative electric potential will attract potassium back into the cell, but it will also attract some sodium, which will enter the cell via transporters and ion channels
- Although the generation of resting potential is heavily drive by potassium ions, it is slightly less negative than the potassium equilibrium potential
- This is because there are other ions involved, such a sodium, which will make the inside of the cell mor positively charged, leading to the resting membrane potential being less negative
- At rest, the membrane 50 times less permeable to sodium than potassium
What are the 2 steps for experimental setup for recording resting membrane potential?
What is the equation for Ohm’s law?
What part of the experiment is related to each variable?
1) KCl filled microelectrodes can be impaled into the cell of interest in saline solution, which allows a current to be injected into the cell (potassium as positive, chloride as negative)
2) We can measure the effect of this change in ionic composition on the resting potential, which can be recorded using an oscilloscope
- Ohm’s law is V=IR (voltage = current/resistance)
- The voltage is the membrane potential measure in the cell (mV)
- The current is what is put into the cell via the microelectrodes
- The resistance in the cells is the ion channels of the cell membrane
- When they’re open, ions can flow, and conductance can be recorded
- When they are closed no ions can pass through
What is the value for: • Resting potential in excitable cells (like neurons) • Resting potential in cardiac cells? • Potassium equilibrium potential • Sodium equilibrium potential
- The resting potential in excitable cells (like neurons) is -70mV
- The resting potential in cardiac cells is around -90mV
- Potassium equilibrium potential is -105mV
- Sodium equilibrium potential is 65mV
What do the following terms mean:
• Depolarization
• Repolarization
• Hyperpolarization
- Depolarization – When membrane potential becomes more positive
- Repolarization – When membrane potential becomes more negative, and goes back towards resting membrane potential
- Hyperpolarization – When membrane potential becomes more negative than resting membrane potential
What occurs if a current (green) is in injected into a non-excitable cell (e.g RBC)?
Why do responses in excitable cells differ?
- If a non-excitable cell is injected with a current, the membrane potential profile will match the profile of the current
- There is depolarization, plateau, then return to membrane potential
- There is a different response in excitable cells, as they have different ion channels on their membrane
Describe how an action potential is generated when excitable cells are injected with a current
- When a current is running through an excitable cell, potassium ions flow out of the cell, leading to a negative membrane potential
- This attracts K+ and Na+ back into the cell, which causes slight depolarization
- When this depolarization reaches a threshold potential, an action potential is generated
What is an action potential?
How are action potentials generated?
When is peak potential reached?
What occurs after peak potential is reached?
- An action potential is rapid depolarization in a cell
- Action potentials are generated by voltage-gated sodium channels
- They are very quickly activated (and inactivated), meaning sodium can quickly flood into the excitable cell, which generates the depolarization of the action potential
• Peak potential is reached around +30mV
- After peak potential is reached, the sodium channels quickly close, preventing any more sodium entering the cell, which results in slight depolarization
- Potassium gated ion channels are slow to activate (and inactivate), and they open as voltage gated ion channels close
- This allows a large number of potassium ions leave the cell, which results in repolarization
- While the voltage gated potassium channels close, there is an overshoot of repolarization, resulting in hyperpolarization of the membrane potential
- After these voltage gated potassium channels close, there is a return to resting membrane potential, which is driven by potassium channels
- Action potentials in neurons are very fast (around 3ms)
- Action potentials in cardiac cells are around 100ms
What are the 5 characteristics of an action potential?
1) The initial depolarization must reach a critical threshold potential
2) Once this threshold is reached, the rapid depolarization takes place
3) The membrane potential depolarizes, and reaches peak potential at around 30mV
4) This response is all or none
5) The membrane potential then repolarises from the peak potential, hyperpolarizes, then repolarizes back to the resting membrane potential
How long do action potentials take to generate in excitable cells and cardiac cells?
What are 3 reasons why action potentials can differ between cells?
How do speeds of permeability change differ in sodium and potassium during the action potential generation?
Why is this?
- Action potentials in neurons are very fast (around 3ms)
- Action potentials in cardiac cells are around 100ms
• Action potentials may differ between cells because of:
1) The function of the cell (different characteristics based on function)
2) Ion channels expressed on the cell
3) Permeability of ions floating into and out of the cell
- There is a rapid increase and decrease of sodium permeability in cells during this process
- There is a slow increase and decrease in potassium permeability in these cells
- This is due to the rapid activation/inactivation of voltage gated sodium channels, and the slow activation/inactivation of voltage gated potassium channels
Describe the change in sodium permeability during the action potential.
Describe the change in potassium permeability during the action potential.
- There is rapid increase in permeability of sodium in the cell due to the opening of voltage gated sodium channels, which drives the rapid depolarization of the action potential
- Once peak potential is reached, there is a rapid decrease in sodium permeability due to closure of voltage gated sodium channels, which results in slight repolarization
- Throughout the process, the voltage gated potassium channels detect this change in membrane potential but are slow to respond
- After the slight repolarization, the voltage gated potassium channels open, resulting in a big increase in potassium permeability of the cell
- This causes many potassium ions to move out of the cell, which causes repolarization
- Since the voltage gated potassium channels are slow to inactivate, this causes slight hyperpolarization
- Once the voltage gated potassium channels close, the potassium permeability of the cell returns to normal, and the resting membrane potential is restored by potassium channels
What is the permeability of sodium compared to potassium at rest?
How does sodium permeability change during the action potential?
How does potassium permeability change after slight repolarization?
- At rest PNa:PK = 1/50
- Action potential associated with sodium permeability increase of 600x
- After slight repolarization, there is a 10x increase in potassium permeability during repolarization
What is the voltage-gated sodium channel?
What does it consist of?
How does it sense changes in membrane potential?
What state are they in prior to the action potential?
When can they open?
What does this allow?
What kind of response is this?
What occurs once peak potential is reached?
How is this different from a closed state?
When can it return to a closed state?
- The voltage-gated sodium channel is a complex integral membrane protein
- It consists of 6 subunits that span the membrane 6 times each
- One subunit has a voltage sensor which detects changes in membrane potential
- Prior to the activation potential, these channels are in a closed, but capable of opening state
- As the membrane potential reaches threshold potential, the rapid activation of these gates occurs,
- The gate undergoes a conformational shape change, which allows for sodium to rapidly enter the cell and cause rapid depolarization
- This is an all or noting response
- Once peak potential is reached, the voltage gated sodium channel converts to an inactive state, where the inactivation gate moves into the channel and blocks the pore
- This inactive state is different from a closed state, as it is not capable of being opened
- The voltage gated sodium channel can’t revert to a closed state till the membrane potential returns to the resting membrane potential
What do voltage gated potassium channels consist of?
How do they sense changes in membrane potential?
What is the key differences between the sodium and potassium voltage gated channels?
When do these channels detect change in membrane potential?
When do they finally open?
What does this allow?
What does slow inactivation cause?
What happens when these channels close?
- Voltage gated potassium channels consist of 4 homologous subunits
- They also have a voltage sensor to detect changes in membrane potential
- The main difference in sodium and potassium gated sodium channels is electivity of ions and speed of inactivation and activation
- When reaching the threshold potential, these channels detect this change in membrane potential and begin to open, but opening is delayed
- It isn’t till around the slight repolarization from sodium channels that the voltage gated potassium channels finally open
- This allows potassium ions to flow out of the cell, leading to repolarization
- Slow activation causes slight hyperpolarization of the membrane potential
- When these channels close, the membrane potential returns to the resting membrane potential, which is driven by potassium channels
What are the 4 stages of positive feedback mechanisms during an action potential?
What stops this positive feedback cycle?
1) Voltage gated Na+ channels open
2) This increases Na+ permeability
3) This increases the flow of Na+ into the cell
4) This results in membrane depolarization
• This positive feedback cycle is stopped by voltage gated Na+ channels closing
