Professor Dave again, let’s look at neurotransmitters.
We just learned all about neurons and action potentials, so we now understand how information
is transmitted throughout the brain and the rest of the body.
Electrochemical activity propagates along an axon, resulting in one of two things.
With an electrical synapse, or gap junction, ions can flow from one cell to the next.
But with a chemical synapse, neurotransmitters are released at the axon terminals, these
interact with receptors on the post-synaptic neuron, and then the signal continues.
But what are these neurotransmitters that traverse the synaptic space?
There are different types, and they serve different functions, so let’s get a closer
look at these now.
While there are a great variety of compounds that qualify as neurotransmitters, let’s
start with the most common ones, which are small molecules of three classes.
These are amino acids, monoamines, and acetylcholine.
We learned all about amino acids in the biochemistry course, and the ones of interest here are
glutamate, aspartate, glycine, and gamma-aminobutyric acid, or GABA for short, which is derived
from glutamate.
Next there are the monoamines.
These are derived from amino acids as well, and they are the most familiar ones.
Dopamine, epinephrine, norepinephrine, and serotonin.
The first three are categorized as catecholamines, while serotonin qualifies as an indolamine.
The catecholamines are all synthesized by enzymes from tyrosine, which is converted
in a series of steps into L-dopa, and then dopamine, and then norepinephrine, and then
epinephrine.
By contrast, serotonin is synthesized from tryptophan.
We can clearly see the differences in structure.
And lastly, we also mentioned acetylcholine.
This is in a class of its own, and it is simply a choline molecule that has been acetylated.
This molecule should be very familiar from our study of the neuromuscular junction in
the anatomy and physiology course, due to its role in promoting muscle contraction.
Apart from these classes of small molecules, there is another class of unconventional neurotransmitters
that don’t fit into the other categories.
This includes small molecules like nitric oxide and carbon monoxide.
These are of a different class, because being extremely small and nonpolar, they are able
to pass through the cell membrane and thus freely diffuse in and out of cells without
needing to pass through membrane proteins.
Once produced inside a neuron, they move into other cells, where they stimulate the production
of second messenger molecules, after which they are quickly converted into something
else, so they are short-lived.
Sometimes these molecules are involved in retrograde transmission, where they travel
from the postsynaptic neuron back to the presynaptic, opposite the direction of travel for other
neurotransmitters.
Another class of unconventional neurotransmitter is the endocannabinoids, which are also retrograde
transmitters.
These are similar in structure to delta-9-tetrahydrocannabinol, the psychoactive agent in marijuana, and also
similar in function, as they all bind to endocannabinoid receptors.
There is also one class of very large neurotransmitters, and that’s the neuropeptides.
These are polypeptide chains, some of which are large enough to qualify as a protein.
Each has a different function, which will depend on the amino acid sequence it possesses,
and they are categorized primarily according to their location in the body.
There are pituitary peptides in the pituitary gland, hypothalamic peptides in the hypothalamus,
brain-gut peptides in the gut, as well as opioid peptides, which resemble opium, and
then all the other miscellaneous ones are grouped into a fifth category.
So those are the basics regarding the various classes of neurotransmitters and their structures.
Let’s also briefly outline some details regarding function.
First, neurotransmitters will tend to exhibit one of two effects when they find their way
into the active site of their respective receptor.
They will either cause excitation or inhibition.
This is kind of like flipping a switch on or off.
More specifically, an excitatory response will be one that results in depolarization
for the post-synaptic neuron, while an inhibitory response will be one that results in hyperpolarization
for the post-synaptic neuron, so it’s the difference between propagating a signal and
halting it.
Some neurotransmitters tend to produce one effect over the other, like the way that glutamate
is typically excitatory, while glycine and GABA are typically inhibitory.
For others, it depends on the context.
Acetylcholine is excitatory at the neuromuscular junction for skeletal muscles but inhibitory
in cardiac muscle.
Next, we must distinguish between direct and indirect action.
Direct action is when a neurotransmitter binds to an ionotropic receptor and opens it up,
so that ions can pass through.
This will affect the membrane potential and promote rapid propagation of a particular
effect.
Acetycholine and the amino acid neurotransmitters tend to behave this way.
Indirect action is when the action is promoted through second messenger molecules, like the
G proteins we discussed in the biochemistry series.
This is similar to the way hormones operate, and the activity is mediated by metabotropic
receptors.
The monoamines, neuropeptides, and small gas molecules will tend to exhibit this behavior,
and when these act as chemical messengers in this manner we sometimes call them neuromodulators.
Now that we are familiar with the small molecules that neurons use to communicate with one another,
let’s zoom out and get a better sense of how these neurons organize themselves.