Chapter 6 - Neurotransmitter Systems

Question 1

Neurotransmitter Criteria

Answer 1

1. Synthesized and stored in presynaptic neuron
2. Must be released by the presynaptic axon terminal upon stimulation
3. 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

Question 2

Immunocytochemistry

Answer 2

The method of anatomically localizing particular molecules to particular cells. Antibodies against a certain molecule are prouced and usually colour labelled.

Question 3

In Situ Hybridization

Answer 3

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).

Question 4

Microionophoresis

Answer 4

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.

Question 5

Neuropharmacological Analysis

Answer 5

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.

Question 6

Ligand-binding method

Answer 6

Using reactively labelled ligands, scientists can map anatomical distribution of different neurotransmitters in the brain.

Question 7

Co-transmitters

Answer 7

Neuron’s that do not obey Dale’s rule and release more than one neurotransmitter type.

Question 8

Choline Acetyltransferase (ChAT)

Answer 8

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.

Question 9

Rate limiting step in ACh Synthesis

Answer 9

Transport of choline into the neuron

Question 10

Acetylcholinesterase (AChE)

Answer 10

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.

Question 11

Catecholamines

Answer 11

Transmitters that contain a catechol. Includes dopamine, norepinephrine and epinephrine (adrenaline)

Question 12

Tyrosine hydroxylase (TH)

Answer 12

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.

Question 13

Rate limiting step in catecholamine synthesis

Answer 13

Activity of tyrosine hydroxylase (TH)

Question 14

Parkinsons Disease

Answer 14

Dopaminergic neurons degenerate and die. A treatment is supplementing DOPA

Question 15

Serotonin

Answer 15

AKA 5-hydroxytryptamine (5-HT), derived from amino acid tryptophan

Question 16

Tryptophan Hydroxylase

Answer 16

Converts tryptophan to 5-HTP by adding a hydroxy group

Question 17

5-HTP decarboxylase

Answer 17

Cleaves a carboxylase off 5-HTP to make 5-HT (serotonin)

Question 18

Limit to serotonin production

Answer 18

The amount of tryptophan available, from blood from diet.

Question 19

Serotonin Reuptake

Answer 19

Serotonin is transported back into the presynaptic terminal where it is either repackaged or broken down by MAO

Question 20

Amino Acid Transmitters

Answer 20

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.

Question 21

Amino Acid Transmitter Synthesis

Answer 21

Synthesized by enzymes from glucose and other precursors in the cell (except for GABA)

Question 22

Glutamic acid decarboxylase (GAD)

Answer 22

GABA is made from glutamate with this enzyme. GABA is degenerated by GABA transaminase

Question 23

Endocannabinoids

Answer 23

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.

Question 24

Structure of transmitter gated channels

Answer 24

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.

Question 25

Amino acid gated channels

Answer 25

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.

Question 26

Glutamate gated channels

Answer 26

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.

Question 27

GABA and glycine gated channels

Answer 27

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).

Question 28

Amine Neurotransmitters

Answer 28

Acetylcholine
Norepinephrine
Epinephrine
Dopamine
Serotonin (5-HT)

Question 29

Amine and amino acid synthesis

Answer 29

Built at presynaptic terminal by precursor molecules being synthesized in transmitter by synthetic enzymes before being packaged by transporter proteins

Question 30

Peptide Synthesis

Answer 30

Synthesized in the soma and transported by axoplasmic transportation. Example peptides are Keffelin and substance P

Question 31

Gray’s Type I Synapses

Answer 31

Asymmetrical (thickening on post-synaptic side is thicker)

Question 32

Gray’s Type II Synapses

Answer 32

Symmetrical, synapses often have flattened synaptic vesicles, often inhibitory

Question 33

Lethal Injection

Answer 33

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.

Question 34

Multiple Sclerosis

Answer 34

Glial cells affected for more than nerve cells. Oligodendrocytes die and circuits stop working (out of temporal coordination problems). Muscle coordination and contraction decreases.

Question 35

Botulism

Answer 35

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).

Question 36

Receptor Potential

Answer 36

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.

Question 37

Nicotinic Receptor agonist and antagonist

Answer 37

Has the agonist nicotine and antagonist curare.

Question 38

Muscarinic Receptor

Answer 38

Has the agonist muscarin and the antagonist atropine.

Question 39

3 Glutamate receptors and their agonists

Answer 39

AMPA (AMPA), NMDA (NMDA), Kainate (kainate, can over excite cell to death)

Question 40

Ligand Binding

Answer 40

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.

Question 41

Molecular Analysis

Answer 41

Can sequence entire chains of amino acids to determine the protein made.

Question 42

Monoamine Oxidase

Answer 42

MAO, found in the external walls of mitochondria. Breaks up amine transmitters which have been transported into cells

Question 43

Transmitter Gated Receptor Structure

Answer 43

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.

Question 44

GABA gated channels

Answer 44

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

Question 45

Metabotropic Receptor Structure

Answer 45

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).