Neurotransmitters

Neurotransmitters

1. acetylcholine

   • in the peripheral Nervous system
     • activates skeletal muscles
       • binds to acetylcholine receptors on skeletal muscle fibres causing the opening of ligand-gated sodium channels and eventually muscle contraction
     • has an inhibitory action on cardiac muscle
       • Ach binds to muscarinic receptors and prevents contraction of cardiac muscles fibres
   • is the major neurotransmitter in the autonomic nervous system and is released in the following areas
     • all pre- and postganglionic parasympathetic neurons
     • all preganglionic sympathetic neurons
       • when the suprarenal medulla is stimulated by Ach it releases epinephrine and norepinephrine
     • some postganglionic sympathetic fibres
       • sudomotor neurons to sweat glands
   • in the central nervous system
     • acts as a neuormodulator upon plasticity, arousal and reward
     • damage to cholinergic system in the brain has been found to be associated with various neurological problems including memory deficits associated with Alzheimers disease
     • promotes REM sleep
     • disruption of Ach may be a primary cause of depression

2. biogenic amines

   • serotonin
   • dopamine
   • norepineprine

3. amino acids

   • GABA - gamma aminobutyric acid
   • glutamate
   • glycine

4. neuropeptides

   • substance P
   • Met-enkephalin

5. gases

   • nitric oxide
   • carbon monoxide

6. Neurotransmitters are secreted in vesicles in the presynaptic terminal, these then fuse with the presynaptic membrane causing them to diffuse across the synaptic cleft

   • neurotransmitters then bind to receptors on the postsynaptic membrane
     • the neurotransmitters can be released by
       • diffusing out of the synaptic cleft
       • being taken up by surrounding cells
       • being degraded by enzymes
       • Thomas Sudhof, 2013 medecine of physiology Nobel prize, for his work on the mechanism of neurotransmitter release from the postsynaptic button
   • there are many different proteins involved in synaptics function including
     • vesicle formation
     • transport of neurotransmitter into vesicles to cytoskeletal elements
     • docking of the vesicles with the presynaptic membrane
     • fusion of the vesicular and cellular membrnae
     • endocytosis of the vesicle membrane for recycling
     • some of those proteins are targets for toxins
       • botulinum toxin and tetanus toxin act on the proteins required for vesicle fusion (SNARE proteins) this blocks the release of Ach at the neuromuscular junction
         • this impairs muscle contraction and causes respiratory failure
         • botulism toxin is used in the medicine Botox this is used for cosmetic purposes to reduce wrinkles and also for treating Dystonia (a neurological disease which causes muscle spasms)

7. can have an inhibitory or excitatory effect depending upon what type of ion channel the ligand binds to

   • if it binds to a K+ or a Cl- channel it will polarise the membrane and therefore an inhibitory effect on the neuron
   • if it bind to an Na+ channel it is going to depolarize the membrane and therefore have an excitatory effect on the neuron
   • neurotransmitters have can different effects on different types of cells