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Synapses

The coordination of cellular activities in animals is usually considered to involve But, in fact, coordination by the nervous system is also chemical. Most neurons achieve their effect by releasing chemicals, the neurotransmitters, on a receiving cell: So the real distinction between nervous and endocrine coordination is that nervous coordination is (Neurotransmitters are chemicals that act in a paracrine fashion.)

The junction between the axon terminals of a neuron and the receiving cell is called a synapse. (Synapses at muscle fibers are also called neuromuscular junctions or myoneural junctions.)

Excitatory synapses

The neurotransmitter at excitatory synapses depolarizes the postsynaptic membrane (of a neuron in this diagram).

Example: acetylcholine (ACh)
Link to further discussion of the electrical events at excitatory synapses.

Inhibitory synapses

The neurotransmitter at inhibitory synapses hyperpolarizes the postsynaptic membrane.

Example: gamma aminobutyric acid (GABA) at certain synapses in the brain. In both cases, the resulting facilitated diffusion of ions (chloride IN; potassium OUT) increases the membrane potential (to as much as −80 mv). This increased membrane potential is called an inhibitory postsynaptic potential (IPSP) because it counteracts any excitatory signals that may arrive at that neuron.

A hyperpolarized neuron appears to have an increased threshold. Actually, the threshold voltage (about −50 mv) has not changed. It is simply a question of whether the depolarization produced by excitatory synapses on the cell minus the hyperpolarizing effect of inhibitory synapses can reach this value or not.

Link to further discussion of the electrical events at inhibitory synapses.

Some neurotransmitters

Acetylcholine (ACh)

Widely used at synapses in the peripheral nervous system. Released at the terminals of Also mediates transmission at some synapses in the brain. These include synapses involved in the acquisition of short-term memory. Drugs that enhance ACh levels — acetylcholinesterase inhibitors — are now used in elderly patients with failing memory (e.g., Alzheimer's patients).

Nicotinic vs. Muscarinic Acetylcholine Receptors

ACh acts on two different types of receptor:

Amino acids

Catecholamines

Synthesized from tyrosine (Tyr).

Other monoamines

Both of these neurotransmitters are confined to synapses in the brain. (However, serotonin is also secreted from the duodenum, where it acts in a paracrine manner to stimulate intestinal peristalsis, and as a circulating hormone, where it is taken up by platelets and also suppresses bone formation.)

Peptides

A selection of 9 of the 40 or more peptides that are suspected to serve as neurotransmitters in the brain. The first six also serve as hormones.

ATP

ATP — probably along with another neurotransmitter — is released at some synapses in the brain.

Synaptic Plasticity

Most neurons release a single neurotransmitter at the synapses at their axon terminals. However, some exceptions have been found.

Turning Synapses Off

Once its job is done, the neurotransmitter must be removed from the synaptic cleft to prepare the synapse for the arrival of the next action potential. Two methods are used:

Drugs and Synapses

Many drugs that alter mental state achieve at least some of their effects by acting at synapses.
Link to discussion of drugs and the central nervous system.

GABA Receptors

The GABAA receptor is a ligand-gated chloride channel. Activation of the receptors increases the influx of chloride (Cl) ions into the postsynaptic cell raising its membrane potential and thus inhibiting it.

A number of drugs bind to the GABAA receptor. They bind at sites different from the spot where GABA itself binds, but increase the strength of GABA's binding to its site. Thus they enhance the inhibitory effect of GABA in the CNS.

These drugs include:

In view of their common action, it is not surprising that they act additively; taken together these drugs can produce dangerous overdoses.

The recreational (and illegal) drug γ-hydroxybutyrate binds to the GABAB receptor.

Catecholamine synapses

Many antidepressant drugs (the so-called tricyclic antidepressants like amitriptyline ["Elavil"]) interfere with the reuptake of noradrenaline and serotonin from their synapses and thus enhance their action at the synapse.

The popular antidepressant fluoxetine ("Prozac"), seems to block only the reuptake of serotonin.

Dopamine synapses

One class of dopamine receptor is bound by such drugs as chlorpromazine and haloperidol. Binding of these drugs leads to increased synthesis of dopamine at the synapse and eases some of the symptoms of schizophrenia.

Synapses blocking pain signals

The two enkephalins are released at synapses on neurons involved in transmitting pain signals back to the brain. The enkephalins hyperpolarize the postsynaptic membrane thus inhibiting it from transmitting these pain signals.

More on Pain

The ability to perceive pain is vital. However, faced with massive, chronic, intractable pain, it makes sense to have a system that decreases its own sensitivity. Enkephalin synapses provide this intrinsic pain-suppressing system.

Opiates such as bind these same receptors. This makes them excellent pain killers.

However, they are also highly addictive.

Electrical Synapses

Electrical synapses are a rare exception to the general rule that neurons signal other neurons by release of chemical neurotransmitters.

Some properties of electrical synapses:
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6 May 2013