Chapter 6 - Neurotransmitter Systems Flashcards
Neurotransmitter Criteria
- Synthesized and stored in presynaptic neuron
- Must be released by the presynaptic axon terminal upon stimulation
- Must show mimicry, experimentally applied chemical must produce response in the postsynaptic cell that mimics the response produced by electrical stimulation of the presynaptic neuron
Immunocytochemistry
The method of anatomically localizing particular molecules to particular cells. Antibodies against a certain molecule are prouced and usually colour labelled.
In Situ Hybridization
A method to confirm if a cell has synthesized a specific protein or peptide. A complementary probe (for the sequence of nucleic acids for the mRNA molecule of protein in question) is made and injected into the neuron’s nucleus. Autoradiogrpahy will reveal if the probe sticks (hybridizes).
Microionophoresis
A method of confirming mimicry. A drug is applied to the membrane of a postsynaptic dendrite and then the postsynaptic neuron’s response is measured and compared to a normal response when the presynaptic axon is electrically stimulated.
Neuropharmacological Analysis
By applying different known agonists to different parts of the body, we can determine what type of receptors are where. For example, ACh receptors come in two varieties, muscarinic and nicotinic, by applying muscarin and nicotin to different parts of the body scientists determine that ACh muscarinic receptors are only on the heart and nicotinic ACh receptors are only on skeletal muscle.
Ligand-binding method
Using reactively labelled ligands, scientists can map anatomical distribution of different neurotransmitters in the brain.
Co-transmitters
Neuron’s that do not obey Dale’s rule and release more than one neurotransmitter type.
Choline Acetyltransferase (ChAT)
Required for ACh synthesis. Adds Acetyl CoA and Choline together (CoA is a byproduct). ACh is made in cytoplasm and packaged into vesicles by ACh Transporters.
Rate limiting step in ACh Synthesis
Transport of choline into the neuron
Acetylcholinesterase (AChE)
The enzyme that breaks ACh down into acetic acid and choline. Not a useful marker for cholinergic synapses as it’s made by non ACh neurons as well.
Catecholamines
Transmitters that contain a catechol. Includes dopamine, norepinephrine and epinephrine (adrenaline)
Tyrosine hydroxylase (TH)
Catalyzes the first step in catacholamine synthesis. Converts tyrosine to L-DOPA (precursor to dopamine, then norepinephrine and finally epinephrine). Adds hydroxy group to tyrosine.
Rate limiting step in catecholamine synthesis
Activity of tyrosine hydroxylase (TH)
Parkinsons Disease
Dopaminergic neurons degenerate and die. A treatment is supplementing DOPA
Serotonin
AKA 5-hydroxytryptamine (5-HT), derived from amino acid tryptophan
Tryptophan Hydroxylase
Converts tryptophan to 5-HTP by adding a hydroxy group
5-HTP decarboxylase
Cleaves a carboxylase off 5-HTP to make 5-HT (serotonin)
Limit to serotonin production
The amount of tryptophan available, from blood from diet.
Serotonin Reuptake
Serotonin is transported back into the presynaptic terminal where it is either repackaged or broken down by MAO
Amino Acid Transmitters
Include glutamate, glycine and GABA. These are the transmitters for most CNS synapses. Glutamate is the major excitatory transmitter in the brain, GABA is the major inhibitory.
Amino Acid Transmitter Synthesis
Synthesized by enzymes from glucose and other precursors in the cell (except for GABA)
Glutamic acid decarboxylase (GAD)
GABA is made from glutamate with this enzyme. GABA is degenerated by GABA transaminase
Endocannabinoids
Retrograde feedback messengers. Not packaged in vesicles, made on demand. Small and membrane permeable. Bind selectively to CB1 cannabinoid receptor, mainly located on presynaptic terminals. Used to avoid post-synaptic cell death by over calcification.
Structure of transmitter gated channels
5 protein subunit (pentamer) channels that are opened by the binding of two transmitter molecules (in this case ACh). They are very precise and sensitive of chemicals and voltage.
Amino acid gated channels
Mediate most of the fast synaptic transmissions in the CNS. The conductance of these channels determines the magnitude of their effects. Properties of these channels are direct effects of their structures. Amino-acid gated channels include glutamate gated channels, and GABA and glycine gated channels.
Glutamate gated channels
There are three types, AMPA, NMDA and kainate. AMPA gated channels are not permeable to Ca but they are to Na and K. NMDA channels are coupled with AMPA, but they are different. NMDA channels allow Na and Ca into a cell (K flows out). They are voltage dependent (because of magnesium block that unplugs with depolarization) and the fact that they allow calcium in means that they can permanently change the neuron, even participate in gene expression and the encoding of memories.
GABA and glycine gated channels
There are two types GABAa and GABAb. GABAa and glycine channels are inhibitory and let in Cl-. This influx of chlorine is increased by the binding of barbiturates and benzodiazepines to the outside of the GABAa receptor (in the presence of GABA!). Certain subunites make the GABAa receptor specific to certain drugs (like ethanol and benzodiazepines) but not others. Neurosteroids are manufactured by the body (including from glial cells and cholesterol) and they have binding sites on GABAa, they’re natural binding may explain why modern drugs have an effect (evolutionarily confusing).
Amine Neurotransmitters
Acetylcholine Norepinephrine Epinephrine Dopamine Serotonin (5-HT)
Amine and amino acid synthesis
Built at presynaptic terminal by precursor molecules being synthesized in transmitter by synthetic enzymes before being packaged by transporter proteins
Peptide Synthesis
Synthesized in the soma and transported by axoplasmic transportation. Example peptides are Keffelin and substance P
Gray’s Type I Synapses
Asymmetrical (thickening on post-synaptic side is thicker)
Gray’s Type II Synapses
Symmetrical, synapses often have flattened synaptic vesicles, often inhibitory
Lethal Injection
Taking away ability to decrease extracellular K takes away ability to fire neuron. Stops the heart and lungs, which is a very painful way to die.
Multiple Sclerosis
Glial cells affected for more than nerve cells. Oligodendrocytes die and circuits stop working (out of temporal coordination problems). Muscle coordination and contraction decreases.
Botulism
Bacteria releases botulin which is a neurotoxin that blocks calcium mediated release of acetylcholine. Any post synaptic cell that receives Ach will be shut down and more importantly certain muscle cells (especially breathing and heart rate).
Receptor Potential
The signal travelling down an axon is converted a receptor potential before entering the pre-synaptic terminal because the pre-synaptic terminal cant receive action potentials.
Nicotinic Receptor agonist and antagonist
Has the agonist nicotine and antagonist curare.
Muscarinic Receptor
Has the agonist muscarin and the antagonist atropine.
3 Glutamate receptors and their agonists
AMPA (AMPA), NMDA (NMDA), Kainate (kainate, can over excite cell to death)
Ligand Binding
Used for mapping where neurotransmitter is found. Doesn’t tell you if it’s at the pre or post synapse. Radiography used to label ligand.
Molecular Analysis
Can sequence entire chains of amino acids to determine the protein made.
Monoamine Oxidase
MAO, found in the external walls of mitochondria. Breaks up amine transmitters which have been transported into cells
Transmitter Gated Receptor Structure
5 subunits, each subunit having 3 or 4 parts (M1, M2, M3 and sometimes M4). Helical loops in the membrane all part of a single protein strand.
GABA gated channels
Selective for Chlorine. There are seperate binding sites for ethanol, neurosteroids etc. This binding sites do nothing on their own, if GABA and ligand are present than the channel becomes extremely efficient. Consuming more than one GABAa ligand at the same time can lead to death
Metabotropic Receptor Structure
7 transmembrane spanning alpha helices. Loops sticking outside receptor have affinity for different ligands and G proteins. Beta-gamma or alpha subunits can activate effector proteins (enzymes usually, not necessarily anchored to membrane).
