HappyMutations:: How neurotransmission takes place

How neurotransmission takes place

30th April 2019

Neurons communicate via neurotransmitters (NTs). These messenger chemicals are synthesised in neuronal cells’ cytoplasm by enzymes and are then transferred to the axon where they are kept in synaptic vesicles until their release.

Figure 1: The body of a neuronal cell showing some of its more important features

Generally, neuronal cells have a balance of ions (negatively or positively charged atoms) that normally keep the intracellular voltage at -70mV; called the resting potential. Regulation is possible with the controlled influx/efflux of the ions which take place with the help of the sodium/potassium pump and facilitated diffusion (see figure below).

Figure 2: The membrane potential of a neuronal cell

The voltage is influenced by changes on the balance of the ions in and out the cell. Slight depolarisations (the inside of the cell gaining positive voltage) cause no effect but when the threshold of -55mV is reached, full depolarisation becomes inevitable and an action potential “fires” (see figure below) bringing the voltage to +30mV.

Figure 3: Voltage of an action potential

Action potentials originate at the start of the axon (the axon hillock) and move along the axon towards the terminals. Its strength is retained with the help of the insulating myelin sheath covering the axon. Along this sheath there are also gaps, where myelin sheath is lacking, which are called Nodes of Ranvier and are rich in voltage-gated ion channels embedded in the cell membrane.

The incoming of the electrochemical charge causes these to open and allow the influx of cations (usually calcium or sodium, depending on the specific channels; though other voltage-gated ion channels also exist) which further depolarises adjacent regions in the cell, with action potentials taking place in the direction from dendrites to axon terminals. Thus the signal is not only retained but also amplified; the process called saltatory conduction. A depolarisation is eventually followed by a repolarisation and a slight hyperpolarisation until the cell returns to its resting potential; all these happen in milliseconds.

Arriving action potentials can also trigger "voltage-gated calcium channels" (VGCCs) in the axon terminals to open, resulting in an influx of calcium ions which in turn bind to special proteins ("synaptotagmins") on the membrane of the NT-filled vesicles which trigger the vesicles to move towards the synaptic membrane. When close enough to the membrane, the vesicular and the synaptic membranes fuse to release the NTs out to the synaptic cleft ("exocytosis").

In the synapse, NTs bind to the receptors on the dendrites of an adjacent neuron, called a postsynaptic neuron because of its position relative to the synapse. Two types of receptors (Rs) exist; metabotropic and ionotropic. Metabotropic Rs (e.g. G protein-coupled Rs) function in inducing cellular responses via secondary messengers like cyclic AMP, diacylglycerol, etc. (see figure below).

Figure 4: A metabotropic receptor like G protein-coupled Rs trigger intracellular responses via secondary messengers

Ionotropic Rs are also called ligand-gated ion channels. These channels open in response to the "ligand" (NT or drug) to allow the passage of specific ions (see figure below) down their concentration gradient. Inhibitory neurons have channels for Cl^- (flowing in) and K⁺ (flowing out) which give a net negative result to the intracellular charge. This causes hyperpolarisation, inhibiting the impulse. Excitatory neurons have channels for Na⁺ (flowing in) and K⁺ (flowing out) but ending up with a net positive charge to the intracellular space. This can build up to the threshold potential in which case a full depolarisation occurs that propagates the impulse.

Figure 5: Ionotropic receptors are ion channels that open in response to ligands to allow the passage of specific ions

When their work is done, NTs are either broken down in the synapse by specialised enzymes, or re-uptaken for reuse by the presynaptic neuron via proteins called transporters (more in Figure 6).

Figure 6: Neurotransmission caused by an action potential