Lecture 2: Electrical Properties of Neurones

Question 1

What is the resting membrane potential (RMP)?

Answer 1

The voltage difference across the neuronal membrane at rest, typically around -70 mV. It results from ionic concentration gradients and selective membrane permeability.

Question 2

How is the membrane potential measured?

Answer 2

Intracellular glass microelectrodes (Ling & Gerard, 1949) are used to measure the voltage inside cells.

The reference electrode is placed outside the cell.

Question 3

Define Hyperpolarisation

Answer 3

Membrane potential becomes more negative.

Question 4

Define Depolarisation

Answer 4

Membrane potential becomes more positive.

Question 5

Which factors influence the resting membrane potential?

Answer 5

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)

Question 6

Julius Bernstein 1880s….

Answer 6

the ionic theory,

the Nernst equation,

semi-permeable membrane

Question 7

Potassium ion movement at resting potential…

Answer 7

• 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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Question 8

Why would the ideal plasma membrane be impermeable to Na+ ions?

Answer 8

So that changing Na+ concentration will not affect resting potential

Question 9

Is there a voltage difference when there is no net ion concentration difference (equal concentration of ions on both sides) ?

Answer 9

No

Question 10

At equilibrium/the resting potential, is there a balance between K+ ions moving in and out of the cell?

Answer 10

Yes

Question 11

Does the electrical gradient simultaneously try to pull K+ back into the membrane?

Answer 11

Yes

Question 12

Nernst Equation

Answer 12

Calculates equilibrium potential for an ion.

Question 13

Goldman-Hodgkin-Katz Equation

Answer 13

Accounts for multiple ion permeabilities.

Question 14

What maintains the ionic gradients at a membrane?

Answer 14

ATP-dependent ion pumps (Na⁺/K⁺ ATPase) maintain ionic gradients.

Question 15

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)

Answer 15

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)

Question 16

What equation can be used to calculate the resting membrane potential (or equilibrium potential for potassium)?

Answer 16

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.

Question 17

What is the Em?

Answer 17

The membrane potential

Question 18

In reality, is there some permeability to Sodium ions at membrane potential?

Answer 18

Yes

Question 19

K⁺ Equilibrium Potential (Eₖ) ~ -80 mV, but Em ~ -70 mV due to…. some Na⁺ leakage.

Answer 19

some Na⁺ leakage. Membrane potential will depolarise and become less negative

Question 20

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.

Answer 20

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.

Question 21

Sodium potassium pump pumps K+ from low concentration outside of membrane to high concentration inside membrane.

Answer 21

Pumps Na+ from inside of cell, where it’s of low concentration, to outside of the cell.

Both require a lot of ATP

Question 22

In reality: membrane potential is usually less negative than EK

Answer 22

In reality: membrane potential is usually less negative than EK

Question 23

What is the action potential?

Answer 23

The action potential is a rapid, transient electrical signal that propagates along the neuron to transmit information.

Question 24

What is Ek in most neurones?

Answer 24

• 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

Question 25

Why does Na+ move into the cell when the voltage gated Na+ channels open (due to action potential causing slight depolarisation)?

Answer 25

- Sodium is diffusing down a concentration gradient - The positive sodium ions are attracted by the negativity inside the membrane (electrical gradient).

Question 26

What are the drivers of moving in and out of membranes?

Answer 26

Concentration gradient and electrical gradient

Question 27

What are the phases of the action potential?

Answer 27

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)

Question 28

What initially depolarises neurones to open the voltage-gated Na+ channels?

Answer 28

- 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.

Question 29

What is meant by the fact that Na+ ion channel opening is regnerative?

Answer 29

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.

Question 30

Main Takeaway:

Answer 30

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.

Question 31

Takeaway:

Answer 31

- 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).

Question 32

Is Na+ channel opening is regenerative?

Answer 32

Yes

Question 33

Is the negative membrane potential needed in order for an action potential to be generated?

Answer 33

Yes

Question 35

What was the key takeaway of the Hodgkin and Katz (1949) experiment?

Answer 35

- 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.

Question 36

Do Na+ voltage gated channels allow for the influx of Na+?

Answer 36

Yes

Question 37

the initial stimulus causes a small change in voltage, which then opens voltage-gated sodium channels.

Answer 37

the initial stimulus causes a small change in voltage, which then opens voltage-gated sodium channels.

Question 39

What is the All-or-None Principle?

Answer 39

If threshold is reached, action potentials are always the same size. Unidirectional Propagation: Ensured by refractory periods.

Question 40

How is the membrane repolarised after an action potential?

Answer 40

(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)

Question 41

Describe ion flow during the action potential

Answer 41

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

Question 42

What 2 things contribute to repolarisation?

Answer 42

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)

Question 43

What model describes how voltage-gated Na+ channels become inactivated?

Answer 43

The ball and chain model

Question 44

Describe Voltage-gated Na+ channel inactivation via the ball and chain mode;

Answer 44

- 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

Question 45

What is the purpose of the refractory period?

Answer 45

To ensure that the action potential travels in ONE direction.

Question 46

Describe the absolute refractory period (ARP)

Answer 46

- 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. -

Question 47

Describe the relative refractory period (RRP)

Answer 47

- 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. -

Question 48

What is universal nerve impulse propagation ensured by?

Answer 48

Ensured by refractory periods.