Lecture 2: Electrical Properties of Neurones Flashcards
Tuesday 7th January 2025
What is the resting membrane potential (RMP)?
The voltage difference across the neuronal membrane at rest, typically around -70 mV. It results from ionic concentration gradients and selective membrane permeability.
How is the membrane potential measured?
Intracellular glass microelectrodes (Ling & Gerard, 1949) are used to measure the voltage inside cells.
The reference electrode is placed outside the cell.
Define Hyperpolarisation
Membrane potential becomes more negative.
Define Depolarisation
Membrane potential becomes more positive.
Which factors influence the resting membrane potential?
Selective membrane permeability (mainly to K⁺ ions).
Ionic concentration gradients:
Inside: K⁺ (125 mM), Na⁺ (12 mM), Cl⁻ (5 mM), Anions (108 mM)
Outside: K⁺ (5 mM), Na⁺ (120 mM), Cl⁻ (125 mM)
Julius Bernstein 1880s….
the ionic theory,
the Nernst equation,
semi-permeable membrane
Potassium ion movement at resting potential…
- The resting membrane potential is the voltage difference across the cell membrane when the cell is not actively sending signals.
- The concentration gradient pushes K⁺ out of the cell because K⁺ naturally moves from high to low concentration.
- The inside of the cell is negative (-80 mV), attracting positively charged K⁺ ions back into the cell.
- At resting potential, the concentration gradient pushing K⁺ out is balanced by the electrical gradient pulling K⁺ back in. This creates a stable resting state where K⁺ movement in and out of the cell is equal.
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Why would the ideal plasma membrane be impermeable to Na+ ions?
So that changing Na+ concentration will not affect resting potential
Is there a voltage difference when there is no net ion concentration difference (equal concentration of ions on both sides) ?
No
At equilibrium/the resting potential, is there a balance between K+ ions moving in and out of the cell?
Yes
Does the electrical gradient simultaneously try to pull K+ back into the membrane?
Yes
Nernst Equation
Calculates equilibrium potential for an ion.
Goldman-Hodgkin-Katz Equation
Accounts for multiple ion permeabilities.
What maintains the ionic gradients at a membrane?
ATP-dependent ion pumps (Na⁺/K⁺ ATPase) maintain ionic gradients.
In moving potassium ions from one side of the cell to another (chemical gradient), and electrical gradient is set up. Opposing electrical force will move Cl- ions to other side of the membrane. (tried to restirct postassium ion movement)
In moving potassium ions from one side of the cell to another (chemical gradient), and electrical gradient is set up. Opposing electrical force will move Cl- ions to other side of the membrane. (tried to restirct postassium ion movement)
What equation can be used to calculate the resting membrane potential (or equilibrium potential for potassium)?
The Nernst equation
- The membrane potential of a cell at rest is typically around -58 mV (close to -60 mV in real neurons). (for potassium alone).
- The Goldman-Hodgkin-Katz (GHK) equation is used to calculate the real resting potential by considering all these ions and their permeabilities.
What is the Em?
The membrane potential
In reality, is there some permeability to Sodium ions at membrane potential?
Yes
K⁺ Equilibrium Potential (Eₖ) ~ -80 mV, but Em ~ -70 mV due to…. some Na⁺ leakage.
some Na⁺ leakage. Membrane potential will depolarise and become less negative
If you only consider potassium (K⁺), you get around -58 mV.
The real resting potential is closer to -70 mV because Na⁺ and other ions contribute.
If you only consider potassium (K⁺), you get around -58 mV.
The real resting potential is closer to -70 mV because Na⁺ and other ions contribute.
Sodium potassium pump pumps K+ from low concentration outside of membrane to high concentration inside membrane.
Pumps Na+ from inside of cell, where it’s of low concentration, to outside of the cell.
Both require a lot of ATP
In reality: membrane potential is usually less negative than EK
In reality: membrane potential is usually less negative than EK
What is the action potential?
The action potential is a rapid, transient electrical signal that propagates along the neuron to transmit information.
What is Ek in most neurones?
- In most neurons, Ek is around -80mV.
- In some cases (e.g., different potassium levels), it may be closer to -58 mV.
- The key takeaway is that
𝐸K is usually more negative than the resting membrane potential because of K+ and potentially Na+ leakage
Why does Na+ move into the cell when the voltage gated Na+ channels open (due to action potential causing slight depolarisation)?
- Sodium is diffusing down a concentration gradient
- The positive sodium ions are attracted by the negativity inside the membrane (electrical gradient).
What are the drivers of moving in and out of membranes?
Concentration gradient and electrical gradient
What are the phases of the action potential?
Resting Potential (~ -70 mV)
Depolarisation (Na⁺ influx through voltage-gated Na⁺ channels)
Repolarisation (K⁺ efflux through voltage-gated K⁺ channels)
Afterhyperpolarisation (AHP) (membrane briefly more negative than RMP)
What initially depolarises neurones to open
the voltage-gated Na+ channels?
- Synaptic transmission: excitatory postsynaptic potentials EPSPs: When a neuron receives excitatory input from another neuron via synapses, neurotransmitters (e.g., glutamate) bind to receptors, leading to a small depolarization called EPSP (Excitatory Postsynaptic Potential).
- Generator (receptor) potentials (sensory neurones): In sensory neurons, stimuli like touch, pressure, or temperature cause a change in the membrane potential.
- Intrinsic properties (eg pacemaker activity in heart): Some neurons and cardiac pacemaker cells spontaneously depolarize due to leaky ion channels or rhythmic activity of specific ion currents.
- Experimental (eg electrical stimulation): In lab experiments or medical settings, neurons can be artificially depolarized using electrical currents.
What is meant by the fact that Na+ ion channel opening is regnerative?
The phrase “Na⁺ ion channel opening is regenerative” refers to a positive feedback loop in which the opening of voltage-gated sodium (Na⁺) channels leads to further depolarization, causing even more Na⁺ channels to open. This process is key to the rapid upstroke of an action potential in neurons.
Main Takeaway:
The axon hillock and axon initial segment (AIS) are critical for action potential initiation due to their high concentration of ion channels and specialized molecular structure.
Once the action potential is generated, it travels down the axon, jumping between nodes of Ranvier in myelinated neurons, ensuring fast and efficient transmission of neural signals.
Takeaway:
- While firing action potentials is passive in terms of immediate energy use, neurons are highly energy-demanding in the long run.
- A constant supply of ATP is necessary to maintain proper neuronal function and prevent the loss of excitability via the Na⁺/K⁺ pump (Na⁺/K⁺ ATPase).
Is Na+ channel opening is regenerative?
Yes
Is the negative membrane potential needed in order for an action potential to be generated?
Yes
What was the key takeaway of the Hodgkin and Katz (1949) experiment?
- Na⁺ is critical for action potentials.
- If extracellular Na⁺ is reduced, depolarization is weaker, proving that Na⁺ influx drives the rising phase of the action potential.
Do Na+ voltage gated channels allow for the influx of Na+?
Yes
the initial stimulus causes a small change in voltage, which then opens voltage-gated sodium channels.
the initial stimulus causes a small change in voltage, which then opens voltage-gated sodium channels.
What is the All-or-None Principle?
If threshold is reached, action potentials are always the same size.
Unidirectional Propagation: Ensured by refractory periods.
How is the membrane repolarised after an action potential?
(a) Resting potential ~ -70 mV
(b) Depolarisation (Na+ moves into neurone via VG Na+ channels)
(c) Repolarisation (Na+ channels close; K+ moves out of neurone via VG K+ channels)
Describe ion flow during the action potential
Around threshold Vm, the membrane becomes much more permeable to Na+ ions
This leads to depolarisation and further recruitment of VG Na+ channels
Depolarisation results in VG Na+ channels inactivation (closure)
After a delay VG K+ channels open
Both contribute to the repolarisation of the membrane after the action potential
What 2 things contribute to repolarisation?
1) Na+ channels close (inactivate)
2) Voltage-gated K+ channels open (after a delay)
Concentration gradient: outward
(125 mM K+ inside , 5 mM K+ outside)
Electrical gradient: outward
membrane potential: positive
Therefore K+ ions move out of the neuron (repolarise)
What model describes how voltage-gated Na+ channels become inactivated?
The ball and chain model
Describe Voltage-gated Na+ channel inactivation via the ball and chain mode;
- Positively charged activation gate (green) keeps channel closed
- Depol of membrane causes activation gate to swing out of the way, allowing Na+ ions to enter and cause further depolarisation
- The inactivation “ball” rapidly enters the channel to block Na+ influx
What is the purpose of the refractory period?
To ensure that the action potential travels in ONE direction.
Describe the absolute refractory period (ARP)
- The absolute refractory period (ARP) is the time during and immediately after an action potential when a neuron cannot fire another action potential, no matter how strong a stimulus is applied.
- Occurs due to VG Na+ channel inactivation.
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Describe the relative refractory period (RRP)
- The relative refractory period (RRP) continues for 2–3 ms after the ARP
- Action potentials can be elicited, but requires stronger or longer stimulation.
- The increased K+ permeability during the RRP makes it harder to depolarise the membrane to activate VG Na+ channels and elicit an action potential.
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What is universal nerve impulse propagation ensured by?
Ensured by refractory periods.
