Action Potentials

1. The Action Potential
2. Voltage-Gated Na⁺ Channels and the Refractory Period
3. Propagation of the Action Potential
4. The Neuromuscular Junction
5. Quiz

• The action potential is the basis of electrical communication in excitable cells such as neurones.
• The neuronal action potential relies on the movement of Na⁺ and K⁺ ions across the cell membrane.
• The action potential is predictable and ‘all or nothing’ in nature.
• The refractory period describes the period of time where the cell cannot generate another action potential.
• Local anaesthetics work by blocking Na⁺ channels.
• The action potential is propagated via the local spread of current which triggers new action potential generation.
• Conduction velocity in neurones is substantially increased via myelination.
• Neurones interact with skeletal muscle cells at the neuromuscular junction.
• Drugs which block the neuromuscular junction can be used as muscle relaxants during general anaesthesia.
• Myasthenia gravis is an autoimmune condition affecting transmission at the neuromuscular junction.

The Action Potential

The action potential describes the phenomenon by which excitable cells create an electrical signal via the movement of ions across the membrane. The key features of an action potential are:

• It relies on ionic gradients - Pre-existing ionic gradients are required for the movement of ions across the membrane. Changing the membrane’s permeability to different ions (i.e. opening and closing ion channels) allows the cell’s membrane potential to be changed.
• It is predictable in nature - Although the shape of the action potential can vary between excitable cell types, in a particular cell type (e.g. a neurone) the action potential should be the same every time.
• It is ‘all or nothing’ - For an action potential to be generated, the voltage across the membrane must reach a threshold level; any lower than this threshold and no action potential will be fired.
• It is propagated without loss of amplitude - The strength of the action potential is maintained along the length of the axon as the local spread of depolarisation triggers new action potentials to be generated.

The action potential relies on the movement of Na⁺ and K⁺ ions. Recall that Na⁺ influx causes depolarisation, whereas K⁺ efflux causes hyperpolarisation.

The stages of the action potential are as follows:

1. Initial stimulus - This is the initial depolarisation that triggers the action potential; it is generally due to the movement of Na⁺, either due to the activation of receptors or the local spread of depolarisation from an adjacent action potential.
2. Depolarisation - If the initial depolarisation reaches the threshold level, around -55 mV, voltage-gated Na⁺ channels (VGSCs) open which results in rapid depolarisation.
3. Repolarisation - After the membrane is fully depolarised, the membrane becomes more negative again as VGSCs become inactivated and voltage-gated K⁺ channels open.
4. Hyperpolarisation - Often the cell ‘overshoots’ the repolarisation phase due to the movement of K⁺, resulting in a brief period of hyperpolarisation before returning back to the resting membrane potential.

Diagram - Graph showing the stages of the neuronal action potential

SimpleMed original by Dr. Joshua Bray

Voltage-Gated Na⁺ Channels and the Refractory Period

The voltage-gated Na⁺ channel is different from other ion channels in that apart from being open or closed, it also has an ‘inactivated’ state. VGSCs become inactivated in response to depolarisation and in this state Na⁺ ions cannot pass through the channel. From the inactivated state, the channel must first ‘recover’ into the closed state before it can be open again. This provides the basis for the refractory period.

Diagram - Voltage-gated Na⁺ channels in the closed, open and inactivated states

SimpleMed original by Dr. Joshua Bray

The refractory period describes the period of time in which the cell cannot generate an action potential. There are 2 terms that you should be familiar with:

• Absolute Refractory Period - Within this period, the cell cannot generate an action potential whatsoever, as all Na⁺ channels are in the inactivated state.
• Relative Refractory Period - In this period, the cell can generate another action potential, although it is harder to do so. This is because the VGSCs are beginning to recover, although some are still inactive. The relative refractory period ends when all Na⁺ channels have recovered.

Local anaesthetics, such as lidocaine, work by blocking Na⁺ channels in small afferent neurones responsible for pain. By blocking these channels, it prevents depolarisation so an action potential cannot be generated. It is often referred to as a ‘use-dependent’ block, meaning that the drug has a preference for blocking Na⁺ channels which are in the open or inactivated state.

Preview the Action Potentials quiz