Neurotransmitters Flashcards
neurotransmitter
- It is synthesized in the neuron.
- It is present in the presynaptic terminal and is released in amounts sufficient to exert a defined action on the post-synaptic neuron or effector organ (e.g., muscle).
- When administered exogenously (as a drug) in reasonable concentrations, it mimics the action of the endogenously released transmitter exactly (for example, it activates the same ion channels or second-messenger pathways in the the post-synaptic cell.
- A specific mechanism exists for removing it from its site of action (the synaptic cleft).
neuropeptides
(short polymers of amino acids), The larger neuropeptides are synthesized only in the cell body. Large transmitters (peptides), once released, must be transported from the cell body to the terminals before they can be released again.
small molecule neurotransmitters
Small molecule transmitters packaged in small lucent vesicles, released via exocytosis at active zones near Ca2+ channels. The best-known neurotransmitters are of this type.
Small molecule neurotransmitters (often single amino acids or amines) can be synthesized in the terminal button.
Therefore, since small transmitters can be resynthesized at the terminals, release can be rapid and sustained.
neurotransmission
E.g., hormones secreted in blood interacts with all cells that have appropriate receptors.
E.g., neurons- release chemical agents, but usually only to specific cells; I.e., the ones with which it forms synapses.
However: neurotransmitters can also be released in a diffuse way as a modulator, with diffuse action,
Or they can be released into the bloodstream as neurohormones.
receptive step
The action of neurotransmitters does not depend on the chemical properties of the transmitter, but on the properties of the receptors that recognize and bind the transmitter.
E.g., in vertebrates acetylcholine (ACh) at the neuromuscular junction is excitatory, but it slows the heart by acting on an inhibitory Ach receptor.
lock and key analogy
German bacteriologist Paul Ehrlich (1900)
Ehrlich supposed that living cells have side-chains in the same way dyes have side-chains which are related to their coloring properties. These side chains can link with a particular toxin (or any antigen), just as Emil Fischer said enzymes must bind to their receptors “as lock and key.”[6]
NT reuptake
Transmitter molecules that do not bind at the time of release to receptors on the post-synaptic cell are removed from the synapse via re-uptake channels.
Inside the pre-synaptic cells the molecules are broken down by monoamine oxydase (MAO), then reconstituted and “repackaged” into vesicles for re-release.
MAO inhibitors therefore block this re-uptake mechanism, and result in allowing excess neurotransmitter to “hang around” in the synaptic cleft (i.e., they increase the available neurotransmitter).
glutamate
Glutamate is the most common excitatory neurotransmitter in the CNS (i.e., opens channels that allow positively charged sodium or calcium ions to enter).
There are several known receptors for glutamate: NMDA, AMPA, kainate receptors, and several metabotropic ones.
NMDA is particularly important for learning and memory, in the process known as long-term potentiation (LTP)
The precursor to glutamate, glutamine, is released by glial cells and transported via special transporter channels from the glial cell into the neuron.
It is metabolized inside the cell body by the mitochondrial enzyme glutaminase.
Once it has been sent to the terminal button and released into the synaptic cleft as a neurotransmitter, the molecules that do not bind to the post-synaptic receptors are taken back into nearby glial cells via re-uptake autoreceptors, then broken down into its precursor and transported into the cell all over again.
Excitotoxicity
Glutamate in high concentrations in the extracellular fluid is highly toxic to neurons, but this occurs with neural injury.
Reduced blood flow to the brain (due to blockage or occlusion – i.e., ischemic stroke) results in atypically high levels of extracellular glutamate. This may be because there is not enough energy (mitochondria require oxygen) for reuptake channels to remove it from the synaptic cleft.
As a result, post-synaptic cells become swollen and the cells die (=excitotoxicity).
Blockade of the post-synaptic glutamate receptors in the post-synaptic cells after injury may prevent their dying;
glutamate receptor antagonists are now being explored as a way to treat ischemic strokes acutely.
GABA
The most common inhibitory neurotransmitter
(i.e., has the effect of opening channels to allow negatively charged chloride ions to enter)
GABA is synthesized from glutamate by an enzyme found exclusively in the GABAergic neurons (i.e. those that secrete GABA as a neurotransmitter), together with a substance which is derived from Vitamin B6.
Thus, dietary deficiency of Vitamin B6 (e.g., in infant formula) can lead to inadequate GABA synthesis.
Since GABA inhibits cells from firing, its absence can lead to epileptic seizures and death.
AcH
Found in many parts of the brain.
In dorsolateral pons, ACh triggers REM sleep
In basal forebrain (nucleus basalis of Meynert), and hippocampus, ACh activates cortex for learning.
Is the only neurotransmitter connecting the nervous system to the muscles via the neuromuscular junction.
There are two types of receptors:
nicotinic receptors (excitatory: leads to influx of Na+ and efflux of K+), these are found in the cortex and also bind to striate muscles or the limbs; and
muscarinic receptors (excitatory or inhibitory) found on smooth muscles such as the heart.
At neuromuscular junction (NMJ), ACh is responsible for all muscular movement (causes muscles to contract).
Nicotine (from tobacco products) binds to nicotinic receptors; curare blocks the nicotinic receptors.
Muscarine (a poison mushroom) stimulates the muscarinic receptor, while atropine (another plant poison) blocks it.
Botulinium = antagonist (a bacterium that inhibits the release of ACh, by attacking fusion protein that allows vesicles to fuse with the membrane and ACh to be released).
catecholamines
Catecholamines are all derived from the same precursor, the amino acid tyrosine, which is manufactured in the liver (with the help of the enzyme phenylalanine).
The first step is to convert tyrosine to L-dopa, which is then converted to dopamine (DA).
From dopamine is derived norepinephrine (NE) (aka noradrenaline).
From norepinephrine is derived epinephrine (E) (aka adrenaline).
dopamine
Dopaminergic neurons are found in (at least) three areas:
in the substantia nigra (black substance), located in the brainstem,
in the ventral tegmental area (medial and superior to the substantia nigra),
in the arcuate nucleus of the hypothalmus.
dopamine systems
Disruption of receptors in different pathways results in different motor, affective, or cognitive symptoms (e.g., nigrostriatal disruption for PD, mesolimbic for mood disorders and addiction, mesocortical for thought disorders).
To summarize:
Nigrostriatal – basal ganglia – movement
Mesolimbic – ventral tegmental to limbic structures – mood
Mesocortical – ventral tegmental to neocortex – thought and memory.
norepinephrine
Synthesized in the locus ceruleus (literally blue place) in the brainstem, below the wall of the 4th ventricle.
Amounts increase during stress due to stimulation from the hypothalamus.
Affects mood, memory, ? Lateral thinking/creativity, hormone production, and cerebral blood flow.
NE depletion affects sustained attention in the face of distraction.
Receptors are all metabotropic, and are sensitive to both epinephrine and norepinephrine. They are referred to adrenergic. They include alpha1 and alpha2 , and beta1, beta2, and beta3. (The latter is found only outside the CNS in fat tissue.) The adrenergic receptors have both excitatory and inhibitory effects, but behaviorally are generally excitatory.
