Neuroscience - Chemical Transmission

Question 0

Criteria for a neurotransmitter

Answer 0

1. synthesized in the neuron
2. present in presynaptic terminal
3. exogenous application mimics endogenous effect
4. there must be a specific mechanism for removal of transmitter

Question 1

Neurotransmitter definition

Answer 1

a small molecule released from a presynaptic cell (to bind with a postsynaptic cell) that forces a change in membrane potential

Question 2

Biochemical steps in synaptic transmission

Answer 2

1. Synthesis
2. Storage and release
3. Binding
4. Removal

Question 3

Describe the 2 types of vesicles

Answer 3

Small vesicles - found in axon terminals, store low molecular weight transmitters, fast transmission
Large dense core vesicles - found in cell body, store neuropeptides, slow transmission

Question 4

What determines how much transmitter is released from a vesicle?

Answer 4

Nothing determines an amount.

If it ruptures, all of the transmitter it stores will be released. It’s all or none.

Question 5

Mechanisms for removal of neurotransmitters

Answer 5

1. Diffusion
2. Reuptake via transporters
3. Enzymatic degradation (acetylcholinesterase is the enzyme)

Question 6

What are the 2 mechanisms by which post synaptic potentials will summate (add together)?

Answer 6

1. Temporal - summation over time at one synapse

2. Spatial - summation from all synapses in the membrane

Question 7

Synaptic plasticity

Answer 7

The potential to change the strength of a synapse

Question 8

Synaptic potentiation

Answer 8

Type of (self) synaptic plasticity that enhances strength of synapse
Due to prolonged pre synaptic activity, increase in release of transmitter

Question 9

Synaptic depression

Answer 9

Type of (self) synaptic plasticity that depresses transmission
caused by release and depletion of transmitter

Question 10

Neuromuscular junction

Answer 10

Synapse between motor nerves and skeletal muscle

Question 11

Lambert-Eaton Myasthenia Syndrome

Answer 11

Antibodies are made to the voltage-gated Ca++ channels; will have less neurotransmitter (Ach) released; leads to muscle weakeness (happens in certain types of cancers)

Question 12

What is the neurotransmitter at the neuromuscular junction?

Answer 12

Acetylcholine (Ach)

Question 13

Botulism

Answer 13

Botulin toxin gets in pre synaptic cell and interferes with the docking of vesicle to membrane

Question 14

Myasthenia gravis

Answer 14

Immune disorder where antibodies are made to attach Ach receptor at the neuromuscular junction (Ach is still released but not enough transmitter available)

Question 15

Ionotropic receptor

Answer 15

Ligand-gated ion channel, provides direct coupling to the ion channel
Neurotransmitter receptor site is on the channel - results in fast synaptic transmission (SSV’s)

Question 16

2 types of post synaptic cell receptors

Answer 16

Ionotropic and Metabotropic

Question 17

Metabotropic receptor

Answer 17

Indirect coupling between the receptor and ion channels
Act through G-proteins (also called G-protein coupled receptors) - involved in slow transmission (LDSV); are often neuropeptides

Question 18

Structure of ligand-gated ion channels (ionotropic)

Answer 18

consists of 5 subunits with 4 transmembrane-spanning domains

Question 19

In excitatory synapses (ESPS), ionotropic channels are permeable to what?

Answer 19

Na, K and Ca (result will be depolarization)

Question 20

In inhibitory synapses (ISPS), ionotropic channels are permeable to what?

Answer 20

Cl- (will lead to hyperpolarization)

Question 21

Differences between excitatory and inhibitory synapses

Answer 21

Excitatory (Gray’s Type 1) - have a wide synaptic cleft (about 30 nm)
Inhibitory (Gray’s Type 2) - have a thinner cleft (<30 nm)

Question 22

Difference in permeability between voltage-gated and ligand-gated ion channels

Answer 22

Voltage-gated: allow only one (type of) ion to pass

Ligand-gated: allow more than one ion to pass (i.e., Na, K and Ca)

Question 23

Differences in regenerative capacity (ability for additional channels to open) between voltage-gated and ligand-gated ion channels

Answer 23

Voltage-gated: capacity is large because only requires a change in membrane potential
Ligand-gated: capacity dependent on the amount of transmitter released (regardless of membrane potential)

Question 24

Toxin that blocks voltage-gated Na channels

Answer 24

Tetrodotoxin (TXX) - comes from the puffer fish

Question 25

Toxin that blocks voltage-gated K channels

Answer 25

Tetraethylammonium (TEA)

Question 26

Toxin that blocks nicotinic Ach receptors

Answer 26

alph-bungarotoxin (from snakes) - blocks at the neuromuscular junction and causes paralysis

Question 27

What are channeopathies?

Answer 27

Diseases or dysfunction of an ion channel associated with neurological disorders (ex: those associated with cystic fibrosis; may be Cl)

Question 28

Structure of metabotropic receptor

Answer 28

1 protein, 7 transmembrane-spanning domains

Question 29

How do metabotropic receptors function?

Answer 29

they link receptor molecules on the membrane to effector molecules inside the cell

Question 30

How do ionotropic receptors function?

Answer 30

Binding causes a conformational change resulting in the opening or closing of the channel

Question 31

What are 2 specific ways that metabotropic receptors work?

Answer 31

1. Alpha subunit directly attaches to ion channel
2. 2nd messengers or protein kinases are used (alpha subunit first binds to an effector molecule (like an enzyme), this produces a 2nd messenger

Question 32

What is a G-protein?

Answer 32

guanine nucleotide-binding protein
it has 3 subunits (alpha, beta, gamma) - binding site is on alpha subunit (will interact with effector molecules or directly with ion channel)

Question 33

Mechanism of activation for G-proteins

Answer 33

1. Resting state - binds GDP
2. Transmitter binds to its receptor - conformational change in the G-protein
3. Results in a conformation change - GDP to GTP; now has energy for alpha subunit to mobilize

Question 34

Changes in channel conductance that are mediated by metabotropic receptors

Answer 34

1. can close ion channels that are normally open
2. can modulate voltage-gated channels (ex: opiates and Ca channels)
3. can modulate both voltage-gated and ligand-gated channels