Neuro 4a – Neurotransmitters

Anil Chopra

  1. Define the essential steps in synaptic neurotransmission. Emphasise the potential for therapeutic intervention in this process.
  • Neurotransmission occurs at SYNAPSE
  • Gaps are around 20nm between presynaptic and postsynaptic membranes.
  • They can be
  • Amino acids (glutamate, gamma amino butyric acid GABA)
  • Amines (noradrenaline, dopamine)
  • Neuropeptides (opioid peptides)
  • These are stored in synaptic vesicles and then docked in the synaptic zone.
  • Requires
  • Ca2+ ions
  • Ready vesicles in pre-synaptic membrane.
  • Complex formation between vesicle, membrane and cytoplasmic proteins. This allows quick vesicle docking and rapid responses to the Ca2+ influx.
  • ATP and vesicle recycling.

Process of Transmission

(1)Action potential reaches membrane.

(2)Causes opening of Ca2+ channels.

(3)Transmitters in vesicles move toward and fuse with the membrane.

(4)Neurotransmitter released into synapse. (Drugs are able to increase release.)

(5)Neurotransmitter diffuses across gap.

(6)Binds to receptor on post-synaptic neurone to bring about effect. (Drugs able to block receptor & activate response)

(7)Transmitter inactivated (drugs able to inhibit enzyme).

(8)Transmitter taken back into presynaptic cell and repackaged.

Synthesis of Transmitters

(1)

  1. Acetylcholine synthesised from choline uptake into nerve terminal.
  2. Dopamine and noradrenaline synthesised from amino acid tyrosine.
  3. GABA (gamma amino butyric acid)
  4. Neuropeptides synthesised in ribosomes

(2)Packaged into vesicles and docked in synaptic zone.Toxins target vesicular proteins.

  1. Explain the differences between the following and give examples.

(i)Excitatory vs. Inhibitory Responses

Excitatory - use glutamate (glutaminergenic)

-influx of Na+ ions

-Depolarise postsynaptic membrane

Inhibitory - use GABA (GABAergic)

-influx of Cl- ions

-Hyperpolarise postsynaptic membrane

(ii)Fast vs. Slow Synaptic Potentials

Fast - effect in μs to ms.

-Ion channel receptors

-Use Glutamate and GABA

Slow - effect in seconds to minutes.

-G-protein coupled receptor

-Use dopamine and acetylcholine

(iii)Ion Channel Receptor vs. G-Protein Receptor

Ion Channel - open up ion channels in postsynaptic

-Can be inhibitory or excitatory

-Use Glutamate and GABA in CNS

-Use Ach at neuromuscular junction

G-Protein - use cAMP as second messenger

-Use CNS and PNS with Ach, dopamine and noradrenaline

  1. Give examples of clinical treatment which acts by:
  2. Increasing transmitter availability or release.

L-DOPA is a precursor to dopamine so boosts production.

  1. Reducing inactivation of transmitter.

Vigabatrin – inhibits GABA transaminase

  1. Increasing activation of receptors.

Benzodiazepines – enhances the action of GABA

Phenobarbital – attaches to GABA receptors.

  1. Blocking receptor function

Those that block glutamate receptors.

  1. Outline the roles of different neurotransmitter systems.

(1)Glutamate converted to Gamma amino butyric acid GABA by glutamic acid decarboxylase.

(2)The GABA is packaged into vesicles.

(3)Released by exocytosis.

(4)GABA diffuses across the synapse.

(5)As it attaches to postsynaptic receptors, it causes and influx of Cl- ions.

(6)GABA is either taken back into the presynaptic neurone via GABA transporters or into glial cells by excitatory amino acid transporter EAAT.

(7)In the glial cell, the GABA is converted to succinic semialdehyde by GABA transaminase.

  1. Explain functional deficit in epilepsy and how it can be treated with drugs that influence excitation and inhibition.

Excess glutamate means over stimulations of postsynaptic neurone which leads to continuous firing of action potentials and can result in a seizure (epilepsy). Anti epileptic drugs can work by:

  • Enhancing the GABA-mediated inhibition of conduction of nerve impulse across a synapse e.g. Vigabatrin.
  • Stopping the inactivation of GABA valporate.
  • Inhibiting glutamate (glutamate antagonists) e.g. Phenobarbital.