Neurotransmitters: Type, Structure, and Function

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.