Action & Postsynaptic Potentials

Question 1

Excitable Cells

Answer 1

Cells that can be electrically excited

Properties:

• electrical current is the flow of ions
• have proteins that form chanels to control ion/current flow
• all cells have the gene for these channels but only excitable cells express them

Examples:

• Muscle cells (e.g cardiac myocytes or skeletal muscle cells) - use flow of ions to generate contraction
• Neurons - use flow of ions to generate action potentials

Question 2

Potential Differences Across Membranes

Answer 2

• Excitable cells must be able to generate & maintain a PD across the membrane by using protein pumps/channels
• Membrane potentials can be between -60v to -80v
• Can be measured by a voltmeter with a microelectrode outside the cell & one inside the cll (through plasma membrane)

How PDs Arise:

• Passive movement of ions - membrane permeability, driving force (electrochemical gradient)
• Active transport of ions - against conc./electrical gradient
• Requires expenditure of metabolic energy by cell

Question 3

Permeability

Answer 3

• Impermeable to an ion - no channels let ion through
• Slightly impermeable to an ion - large driving force required
• Readily permeable - small driving force required

At rest:

• fairly readily permeable to K⁺ & Cl^-
• poorly permeable to Na⁺
• impermeable to various large organic anions

Question 4

Origin of Resting Potentials

Answer 4

There is always a voltage difference & uneven distribution of charge on a membrane, even at rest

Due to:

• selective permeability of the cell membrane to different ions
• unequal distribution of ions across the membrane - maintained by Na⁺/K⁺ pump (3 in, 2 out)

Electrochemical gradient = combined chemical (concentration) & elecrtical (charge) gradient - usually cancel each other out, no net movement

Question 5

Ionic Basis of an Action Potential

Answer 5

1. Stimulus (-70mv to - 55mv) - EPSPs via neurotransmitters cause some Na⁺ gated-channels to open
2. Threshold Potential (-55mv) - all or nothing
3. Depolarisation - all Na⁺ ion channels open, less negative membrane potential
4. Action Potential (+30mv) - action potential generated & Na⁺ channels close. K⁺ channels are fully open at -25mv
5. Repolarisation - K⁺ channels are fully open & Na⁺/K⁺ pumps open to restablish resting potential
6. Hyperpolarisation (-90mv) - over correction to stop action potentials happening too quickly, K⁺ channels close
7. Resting potential (-70mv)

Question 6

Stimulus to Threshold Potential

Answer 6

• Dendrites receive signals from other neurons via neurotransmitters - binds to ligands & act as chemical signal
• Causes ligand-gated ion channels to open
• Allows charged ions to flow in & out
• Now an electrical signal: EPSP or IPSP

EPSP - net influx of positive charge

IPSP - net influx of negative charge or efflux of positive charge

• If enough EPSP happen at once, there will be a bigger effect on the cell’s charge
• Threshold potential - all or nothing
• If charge reaches -55mv, an action potential can happen

Question 7

Depolarisation to Action Potential

Answer 7

Once threshold potential is reached:

• triggers voltage-gated Na⁺ channels to open at the axon hillock (respond to change in v)
• sodium rushes in (depolarisation), chain reaction down entire length of axon
• neuron has fired the action potential - membrane is now +30mv relative to external environment due to depolarisation

Question 8

Absolute Refractory Period & Repolarisation

Answer 8

Absolute refactory period (+30 to -55mv)

• Innactivation gate blocks the sodium-gated channel - impossible to generate another action potential (won’t respond to any stimuli)
• Keeps the action potentials moving in one direction
• Stops the action potentials happening to close in time

Repolarisation

• Potassium voltage-gated channels (slow to respond) are fully open - K⁺ moves out of the cell
• No inactivation gate - stays open for longer
• Sodium-potassium pumps move 2 K⁺ in, 3 Na⁺ out (more postive ions out than in)
• Cell becomes more negative (closer to resting potential) to blunt the effects of sodium depolarisation

Question 9

Relative Refractory Period & Hyperpolarisation

Answer 9

Relative Refractory Period

• sodium channels closed but no longer innactivated (around -55mv)
• Would take a stong stimulus for them to re-activate (depolarise) when the cell is hyperpolarised - need more ions to meet the threshold

Hyperpolarisation

• due to slow closing of potassium voltage-gated channels & efforts of S/P pumps, small period of overcorrection
• stops the action potentials happening too close together
• as potassium channels close, the cell returns to resting potential

Question 10

Changes to Ionic Permeability

Answer 10

During action potential, ionic permeabilities are the opposite to that of the resting potential:

• membrane is very permeable to Na+ - more Na⁺ inside than outside (depolarisation)
• membrane is relatively permeable to K+ - less K⁺ inside (repolarisation - channels vs pumps) than at resting potential

Question 11

Convergence/Divergence

Answer 11

Convergence = multiple impulses that converge into one on a single neuron (rod cell - eye)

Divergence = one impulse in, multiple neuron branches out (motor neuron to a group of muscles)

Question 12

Summation of Post-Synaptic Potentials

Answer 12

A) Subthreshold, no summation = single EPSPs do not increase membrane potential enough to fire an action potiental

B) Temporal summation = timely impulses, one after the other reaches threshold - action potential fires

C) Spatial summation = more than one EPSP impuluse simultaneously on the same neuron - strong enough to meet threshold

D) Spatial summation of EPSP & IPSP - cancel each other out, no effect on membrane potential so no action potential fired

Question 13

Propagation of Action Potentials

Answer 13

• Fatty myelin sheath - from glial cells like schwann/oligodendryctes
• Myelin insulates axons to increase conduction velocity - there are no channels within the myelin sheath
• Nodes of Ranvier - non-myelinated cells form gaps between myelin sheath
• Propagation of action potentials take place at the Nodes of Ranvier (as there are channels)
• Saltatory conduction - charges essential jump/bump between node to node, speeds up conduction

Question 14

Conduction Velocity

Answer 14

Nerve fibres are classified according to:

• diameter - less resistance, faster flow
• degree of myelination - insulation increases velocity of conduction

Axon types:

• A-alpha (propriception) - most myelination, largest diameter
• A-beta (propriception)
• A-gamma (sharp pain)
• C - (dull pain, throb, ache) - less myelinated, smallest diameter

Question 15

Accomodation

Answer 15

• Maintained depolarisation leads to a higher threshold
• Most likely due to inactivation of Na⁺ channels - few channels to potentially open, threshold changes
• Overstimulation of axon - switch off
• Phenomenon - means our body stops responding to certain stimuli after a certain period of time e.g clothes or itch
• Alters propriception - awareness of external environment

Question 16

Clinical Relevance of Action Potentials

Answer 16

Local Anaesthetics e.g Lignocaine

• increases threshold of firing
• prevents the initiation of an action potential by blocking Na⁺ channels
• Fine nerve fibres are most sensitive - those involved with pain (A-gamma & C)

Epilepsy

• dysfunctional sodium channels (open too quickly/at different thresholds) or potassium channels (slows efflux)
• can lead to overstimulation - too many action potentials fired
• results in seizures

Toxins e.g Tetrodotoxin (TTX)

• neurotoxin found in puffa fish
• increases threshold of firing
• specifically blocks Na⁺ channels
• no action potential fired as there is no initial influx of Na⁺

Question 17

Cross Section of a Nerve

Answer 17

Endoneurium: connective tissue surrounding a nerve fibre

Perineurium: surrounding a fasicle or group of fibres

Epineurium: surrounds the entire nerve

• endoneurium acts to selectively allow molecules to pass into the endoneurial fluid around each fibre
• volume of this liquid increases with nerve irritation

Question 18

Compound Action Potentials

Answer 18

• Measuring action potentials from a single axon is too complicated & requires highly specialised equipment
• Activity of whole nerves is recorded externally using surface electrodes instead - gives the summed activity of all action potentials in the nerve
• Summed action potentials = Compound Action Potentials (CAPs)
• Arise from extracellular stimulation of the nerve, recorded by extracellular electrodes
• Potential difference between two electrodes is recorded with extracellular surface electrodes
• Basline recording - no potential difference between the two electrodes in the absence of a stimulus
• When a stimulus is applied, a wave of depolarisation passes down the nerve - first electrode. becomes negative to the more distal electrode
• Difference is shown by a positive deflection in the recording
• When the wave reaches the second electrode, it becomes more negative compared with the more proximal electrode - shows as a negative deflection in the recording

Question 19

Threshold Voltage

Answer 19

• Amount of stimulation required to produce an action potential in a nerve
• Depends on the axon diameter - large diameter stimulated at lower voltages than smaller diameter axons
• CAPs represent the ‘all or nothing’ action potentials only from those actions that are stimulated at that particular voltage
• As the simulus voltage increases, more & more axons will be excited until all are
• Therefore, the magnitude of the CAP will increase with increased stimulus strength
• After the maximum response is obtained, further increases in stimulus (supramaximal stimuli) will have no further effect on CAP magnitude
• As Axons have different diameters so different conduction velocities, as more & more axons are excited, the shape of the CAP will alter

Question 20

Recording Peripheral Nerve Activity

Answer 20

Sensory Nerve Activity

• usually recorded by stimulating the fingers or toes, recording over the nerves proximal to stimulation
• example: stimulate ring finger & record the nerve response over the median nerve above the wrist
• Disadvantage - electrical signal is tiny (just a few uV) & a large amount of stimuli must be delivered and averaged to produce a reliable estimate

Motor Nerve Activity

• can be recored much more readily - stimulating a peripheral nerve & recording the resultant actvity in a muscle supplied by that nerve
• Common approach is to stimulate the median nerve at the wrist & record consequent electrical activity over the abductor pollicis brevis in the thumb

Question 21

Measuring Nerve Conduction Activity

Answer 21

• Electromyography
• Small electrical current is applied over a motor nerve & contraction of a muscle is measured (by flat electrodes on the skin)
• Small electrical current can be applied more proximally over the same motor nerve
• Distance between stimulation sites is measured & divided by the difference in latency (or delay) between muscle contractions, giving nerve conduction velocity (m/s)
• Time it takes for the muscle to contract = evoked potential
• Maximum voltage when all the axons are stimulated = supramaximal response
• Conduction velocity (speed of the response) in motor nerves is approx 50-60m/s average

Question 22

Factors that Affect Conduction Velocity

Answer 22

Increases Nerve Conduction Velocity

• Increase in nerve diameter
• Increase in temperature

Decreases Nerve Conduction Velocity

• Blocking sodium channels with tetrodotoxin
• Loss of myelination
• Immersion in ice-cold water

Question 23

Physiological Events that Occur During Latency

Answer 23

1. Electrical stimulus generates an action potential in median nerve
2. Action potential is conducted along the nerve axon to the neuromuscular junction
3. Acetylcholine (ACh) is released into the synaptic cleft
4. ACh diffuses across synaptic cleft
5. ACh binds to ‘nicotinic’ acetylcholine receptors on the motor endplate, leading to depolarisation
6. Initiation of an action potential that spreads across the motor unit
7. Action potential stimulates a release of calcium ions from the sacroplasmic reticulum
8. Increased cellular calcium levels start the biochemical events that underlie contraction

Question 24

Peripheral Neuropathies

Answer 24

• Various combinations of motor, sensory & autonomic dysfunction
• Motor problems include weakness, cramps, spasms, muscle wasting & fasciculations (twitching)
• Sensory symptoms include both loss of sensations & disordered sensations with tingling, numbness & heightened sense of pain
• Autonomic involvement may mean balance is impaired, abnormal blood pressure/heart rate, decreased ability to sweat, constipation/diarrhea, incontinence or sexual dysfunction
• Motor neuron disease is distinguished from peripheral neuropathies as there are no sensory or autonomic symptoms/signs

Question 25

Mononeuropathy

Answer 25

• Affects only a single nerve
• Usually caused by a localised trauma, compression or infection
• Carpal tunnel syndrome is an example of a mononeuropathy - median nerve is compressed beneath carpal tunnel in hand

Question 26

Mononeuritis Multiplex

Answer 26

• Results from damage to several different nerves that can occur either at the same or different times
• Usually an acute or subacute loss of motor & sensory functions in the affected nerves, associated with pain
• Example condition is diabetes mellitus, polyarteritis nodosa (inflammatory disease of blood vessels) or rheumatoid arthritis

Question 27

Polyneuropathy

Answer 27

• Commonly first affects the limb extremities, often starting in the foot & spreading upwards in the leg, before affecting the fingers & speading up into the hands/arms
• Polyneuropathies are commonly associated with generalised diseases
• Most common cause diabetes mellitus
• Was associated with pernicious anemia before vitamin B₁₂ therapy
• May also be associated with chronic alcohol syndrome
• Guillian-Barre syndrome - an acute infection causes an autoimmune destruction of myelin sheaths with a rapidly progressing polyneuropathy
• Treatment with plasmapheresis or intravenous immunoglobulins allow most suffers to make a complete recovery