Synapses

A synapse consists of
- Presynaptic neurone
- Synaptic gap
- Postsynaptic neurone
Chemical transmitters are made and stored in the presynaptic terminal
Transmitters are stored in cytoplasmic vesicles
Dictates that transmission across a synapse is in only one direction

Transmitters are released by an action potential
Transmitter release requires calcium ions
The action potential arriving in the terminal axon opens calcium channels
Intracellular calcium is increased
Calcium causes vesicles to fuse to the membrane
They open up and the transmitter is released
Transmitter diffuses across the synaptic gap and binds to a post-synaptic receptors
The synaptic gap is short and the transmitter travels across it by simple diffusion
The transmitter binds to a specific receptor protein in the postsynaptic membrane
When transmitter binds to a receptor it produce a change in membrane potential
Depolarisation is know as an excitatory postsynaptic potential (EPSP)
Hyperpolarisation is know as an inhibitory postsynaptic potential (IPSP)
Most transmitters produce EPSPs - acetylcholine, adrenaline and noradrenaline
The major transmitters producing IPSPs are glycine and GABA
There are both excitatory and inhibitory nerves coming into most synapses
If there are enough EPSPs the postsynaptic membrane will be depolarized to the threshold level
An action potential will be produced and a signal will transmit along the postsynaptic nerve
Once the signal has been delivered the transmitter is removed
In some cases the transmitter is broken down by an enzyme in the synapse
In other cases the transmitter is taken back up into the presynaptic neurone

Acetylcholine (ACh) is a simple molecule synthesized from choline and acetyl-CoA
This occurs through the actions of choline acetyltransferase
Neurons that synthesize and release ACh are termed cholinergic neurons
Destroyed by hydrolysis using the enzyme acetylcholinesterase
ACh receptors are ligand-gated cation channels
Two main classes of ACh receptors have been identified muscarinic and nicotinic receptors
Both receptor classes are abundant in the human brain
Nicotinic receptors are further divided into those found at neuromuscular junctions and those found at neuronal synapses
Numerous compounds have been identified that act as either agonists or antagonists of cholinergic neurons
The principal action of cholinergic agonists is the excitation or inhibition of autonomic effector cells
The responses of cholinergic neurons can also be enhanced by administration of cholinesterase (ChE) inhibitors

The principal catecholamines are noradrenaline, adrenaline and dopamine
These compounds are formed from phenylalanine and tyrosine
Tyrosine is produced in the liver from phenylalanine through the action of phenylalanine hydroxylase
The tyrosine is then transported to catecholamine-secreting neurons
A series of reactions convert it to dopamine, to noradrenaline and finally to epinephrine
Catecholamines exhibit peripheral nervous system excitatory and inhibitory effects
The catecholamines bind to two different classes of receptors
These are termed the alpha- and beta-adrenergic receptors
The adrenergic receptors are classical serpentine receptors that couple to intracellular G-proteins
Noradrenaline released from presynaptic noradrenergic neurons is recycled in the presynaptic neuron by a reuptake mechanism

Serotonin (5-hydroxytryptamine, 5HT) is formed by the hydroxylation and decarboxylation of tryptophan
The greatest concentration of 5HT (90%) is found in the enterochromaffin cells of the gastrointestinal tract
Most of the remainder of the body's 5HT is found in platelets and the CNS
Neurons that secrete 5HT are termed serotonergic
Following the release of 5HT some is taken back up by the presynaptic serotonergic neuron
The function of serotonin is exerted upon its interaction with specific receptors
Several serotonin receptors have been cloned and are identified as 5HT1, 5HT2, 5HT3, 5HT4, 5HT5, 5HT6, and 5HT7
Some of these receptor types have subgroups
Most of these receptors are coupled to G-proteins that affect the activities of either adenylate cyclase or phospholipase C
Some serotonin receptors are presynaptic and others postsynaptic
- 5HT2A receptors mediate platelet aggregation
- 5HT2C receptors are important in control of food intake
- 5HT3 receptors are present in the gastrointestinal tract and are related to vomiting
- 5HT6 and 5HT7 receptors are distributed throughout the limbic system
- 5HT6 receptors have high affinity for antidepressant drugs

Several amino acids have distinct excitatory or inhibitory effects upon the nervous system
GABA is an inhibitor of presynaptic transmission in the CNS
GABA is formed by the decarboxylation of glutamate catalyzed by glutamate decarboxylase
GABA exerts its effects by binding to two distinct receptors, GABA-A and GABA-B
The GABA-A receptors form a chloride channel
The binding of GABA to GABA-A receptors increases the chloride conductance of presynaptic neurons
The benzodiazepine family of drugs exert their effects by potentiating the responses of GABA-A receptors to GABA
The GABA-B receptors are coupled to an intracellular G-protein
Act by increasing conductance of an associated potassium channel

Synapses and neuromuscular junctions