Nerves and the Neuromuscular Junction

The resting membrane potential

This is the steady state voltage across the cell membrane at rest, which is determined by:

  • The ions present and their concentrations
  • Membrane permeability to those ions
  • Ion pumps that alter concentration gradients

In most neurones this is around -70mV and is largely maintained by:

  • Na-K ATPase
    • 3 sodium ions out, 2 potassium ions in
  • Membrane is 100x more permeable to potassium than sodium so potassium leaks out down its concentration gradient
  • Donan effect
    • Phosphates and proteins are negatively charged and remain within the cell, further increasing the negative charge

The peripheral nerve action potential

An action potential refers to the depolarization of any excitable cell as a result of a stimulus such as a ligand binding or a voltage gated channel opening.

There are four phases to the peripheral nerve action potential:

Phase 1

The resting potential of -70 mV rises towards the threshold potential of -55 mV.

Phase 2

At this point large numbers of voltage-gated sodium channels open and an all-or-nothing action potential begins, causing a depolarisation and rise in membrane potential to +30 mV.

Phase 3

Sodium channels close and potassium channels open, allow potassium to leave the cell, causing rapid repolarisation.

Phase 4

The repolarisation ‘overshoots’ causing hyperpolarisation before the sodium-potassium pump restores the resting membrane potential.

What are the types of refractory period?

  • Absolute and Relative
    • Absolute refractory period is the duration of time after an action potential where another action potential cannot be conducted, no matter the stimulus applied
      • During this time the membrane potential is more positive than the threshold
  • Relative refractory period is where a second action potential could be transmitted but it would need a supramaximal stimulus
    • This occurs during the period of hyperpolarisation until the resting baseline potential is restored

What is the effect of hypokalaemia?

  • Remember that potassium is a primarily intracellular ion
    • Hypokalaemia can be acute or chronic
      • Acute hypokalaemia
        • The extracellular potassium decreases, causing an increased concentration gradient
          • The cell becomes hyperpolarised and less excitable
            • This leads to reduced conductivity for action potentials
              • Hence muscle weakness is a symptom
      • Chronic hypokalaemia
        • The intracellular potassium has had time to redistribute and restore the correct concentration gradient
          • Muscle weakness is therefore not such an issue

What are the different types of nerve fibres?

  • Myelinated fibres demonstrate saltatory conduction, where the action potential ‘jumps’ from one node of Ranvier to the next, making them faster

What would an action potential look like in a compound nerve made up of all the different types of nerve fibre?

  • Different nerve fibres have different diameters, degrees of myelination and therefore conduction velocities
    • If a supramaximal stimulus is applied then all of the fibres will depolarise but conduct at different velocities

What is the Nernst equation?

  • This will calculate the theoretical resting membrane potential for just that ion
    • Chloride is -70 mV
    • Sodium is 60 mV
    • Potassium is -90 mV

What is the Goldman equation?

  • This is essentially the Nernst equation applied to all the relevant ions acting across the membrane at the same time

What is the Gibbs-Donnan effect?

  • The behaviour of charged particles across a semi-permeable membrane
    • Particles will move down a concentration gradient until the electrochemical potential opposing it increases sufficiently to produce a balanced equilibrium
      • The voltage or potential across the membrane at this point is the equilibrium potential
        • This can be deduced using the Nernst equation

Describe the neuromuscular junction

  • A chemical juntion between the motor neurone and the muscle
  • Each muscle fibre receives a single axon branch from the Aα neurone
  • The post synaptic membrane has a folded appearance with peaks and troughs
    • The peaks have the acetylcholine receptors to induce muscle contraction and the troughs containe acetylcholinesterase
  • Acetylcholine is produced from acetyl-coA and choline and stored in presynaptic vesicles, with approximately 10,000 molecules per vesicle
  • Some of these vesicles are ‘deep’ in the neurone and others are clustered near the post synaptic membrane in ‘active zones’
    • Depolarisation causes voltage gated calcium channels to open, leading to release of these vesicles
      • Approximately 2 million molecules of ACh are released each with each action potential

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