Neurophysiology

Resting membrane potential

The difference in electrical potential between the intracellular space of a neuron (-65 to -70 mV) and outside the cell

→ due to a phospholipid bilayer, impermeable to ions (aq)

Pumps vs channels

Pumps are proteins that ACTIVELY transport ions against their concentration gradient, requiring energy (Na/K and Ca)

Vs

Channels are proteins that allow certain ions to move across membrane = rapid movement, contributing to mV and APs

• Voltage-gated = open/close in response to changes in mV

• Ligand-gated = open/close in response to NT binding

• Leak channels = always open, passive flow
  

Steps of an action potential

1. Neuron is at resting membrane potential

2. Depolarising stimulus arrives (NT or change in mV)

3. Membrane depolarises to threshold → VGSC open & Na enters

4. Rapid Na entry depolarises the cell

5. At peak, VGSC close and VGPC open gradually in response to depolarisation

6. Potassium moves from cell to extracellular fluid

7. K channels remain open, and additional K anions leave the cell, hyperpolarising it

8. VGPC close, and rate of K leakage reduces

9. Cell returns to RMP and resting ion permeability

Significance of a neuron reaching threshold

Synaptic potentials (EPSPs and IPSPs) are graded, and can summate to reach threshold, where a neuron is depolarised enough to trigger an all-or-nothing action potential, and open VGSCs.

Why are action potentials are said to be ‘all or none’?

Once threshold stimulus is reached, an AP will occur fully, versus not at all. The AP propagates along the neuron without a decrease in magnitude

Significance of the axon hillock in APs

• Integration centre: for all the inhibitory & excitatory signals received at the synaptic bouton (dendrites and cell body)

• Threshold determination: high VGSC density = high sensitivity to changes in mV, it’s easiest to begin an AP here

• Initiation: AP propagates from here, down the axon to other neurons or muscles

Absolute and relative refractory periods (+ physiological basis)

Action potential
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Absolute refractory period = impossible to fire more APs, as the VGSCs are either open, opening, or inactivated (prevents reverberation)
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Relative refractory period = Harder than usual to drive an AP, only with a bigger depolarising stimulus. Some VGPCs are still open, causing hyperpolarisation.

Myelinated vs non myelinated axons

APs face the following issues during propagation:

1. Loss of local circuit through ion leakage channels

2. Axoplasmic resistance against depolarising currents (axon size)

3. Electrical resistance (discharging of large charges on membrane)

Unmyelinated axons:

• AP can only propagate on membranes with high VGSC density

• Each channel has to slowly be sequentially depolarised

• Can go in the reverse direction, as refractory period is shorter

Myelinated axons

• Myelin blocks leakage of current between nodes of ranvier

• Myelin insulates the axon to prevent charge buildup and current can easily spread to next node (no resistance)

• Propagation is much faster as AP can jump to VGSCs in nodes

• Less ion exchange = more energy efficient

Synaptic structure and function

Presynaptic neuron → recieves a propagating AP, and opens VGCC, allowing Ca²⁺ to enter the cell

• Synaptic vesicles: sacks filled with NT

• Axon terminal: NT vesicles are released into synaptic cleft in response to depolarisation

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Synaptic cleft: gap ~20-40 nm → NT diffuses across cleft to postsynaptic neuron

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Postsynaptic neuron: has receptor proteins for diffusing NTs to bind to, intiating a response
→ ion channels on the postsynaptic membrane open/close, changing its mV to excite or inhibit this neuron

Steps of synaptic transmission

1. AP arrival down the axon of the presynaptic neuron

2. CGCCs open and influx of calcium occurs to depolarise

3. Depolarisation triggers synaptic vesicle release and fusion with the presynaptic membrane to release into synapic cleft

4. NTs diffuse across cleft and bind to speific receptors on postsynaptic membrane

5. Post synaptic rexponse → NT binding can open/close ion channels, changing the postsynaptic neuron’s membrane potential (excitation OR inhibition)

6. NT action is terminated via: reuptake into presynaptic neuron, enzyme degredation, diffusion away from synapse

Synaptic potential summation

Multiple inputs contributing to neuron mV threshold

• Temporal summation: when multiple APs arrive at a single synapse in rapid succession leading to a larger change in mV

• Spatial summation: when multiple PSPs from different synapses combine if close enough in time and space → each release NTs at different synapses on the same neuron

What ions are responsible for determining mV in resting conditions?

Intracellular: K⁺, Org^-

Extracellular: Na⁺, Cl^-

Resting membrane potential (V_m) vs Equilibrium potential (in excitable cells)

E_ion [given by Nernst equation]: membrane potential at equilibrium, when no ions are flowing in and out of a (hypothetical) cell (only permeable to one ion)

V_m: The steady-state difference in voltage when the cell is at rest, determined by the relative permeabilities and concentrations of K, Na & Cl