There are many different types of neurotransmitter substances in our nervous system. The most well known are acetylcholine, adrenaline, noradrenaline, dopamine, serotonin and GABA (gamma-amino butyric acid). These are found throughout the brain in different areas. However, some brain regions may have more of one type than another. Some neurotransmitters are also found in the peripheral nervous system synapses.
Each neurotransmitter substance has its own specific receptors. Importantly, for each type of receptor there are several sub-types. Let’s look at the norepinephrine (also called noradrenaline) neurotransmitter as an example. Norepinephrine acts on the norepinephrine receptor. But, in fact, there are two main types of this receptor named alpha and beta. To make matters more complex, for each of these, there are several sub-types, such as alpha1, alpha2, beta1, etc. Each sub-type of receptor has its own distribution within the nervous system and consequently has different actions. Also, the relative ability of norephinephrine to bind to these receptor sub-types also varies.
A neurotransmitter’s effect on the postsynaptic cell may also vary. In one synapse, a given neurotransmitter substance may have a stimulating effect on the postsynaptic nerve cell, whereas in another synapse, elsewhere in the brain, for example, the same neurotransmitter substance may have the opposite effect. This difference is often driven by the type of receptor found on the post-synaptic membrane at a given synapse.
Many drugs that act on the nervous system do so by interacting with the synapse. For example, one of the structures in the brain, known as the substantia nigra contains nerve cells that make extensive use of dopamine as a neurotransmitter substance. In Parkinson’s disease these neurones are destroyed. Therefore, the treatment for this disease involves a drug that contains a substance that the brain can convert into dopamine.
Another example of a group of drugs that alter synaptic transmission are the SSRIs (selective serotonin reuptake inhibitors). These drugs are given to people with various forms of depressive disorders. SSRIs inhibit the re-uptake of serotonin from the synapse after it has been released in the synaptic cleft. Accordingly serotonin acts longer on the postsynaptic nerve cell receptors and its effects on these cells are increased.
Different drugs that mimic the action of neurotransmitters will also have a differential ability to bind to different sub-types of receptors. These differences can be exploited therapeutically to preferentially stimulate or block different actions of neurotransmitters. However, it is not like that a type of receptor will only be found in one location or have one action. This partly explains why drugs often have side effects.
In this chapter we have described what a nerve impulse is. We have learned that this is controlled by the movement of sodium and potassium ions in and out of neurones and axons. We have discussed the ways in which nerve cells communicate together using neurotransmitters released into the synaptic cleft and that these have either a stimulating or inhibiting effect on the postsynaptic neurone. The postsynaptic neurone is regulated by several thousand such synapses at any time, and it is the sum of stimulatory and inhibitory synapses at any given time that determines whether the postsynaptic neurone will reach the threshold membrane potential to generate a new nerve impulse.