Lecture 6 Flashcards
What are three classes of neurotransmitters?
Amino acids, amines, peptides
What are the different types of neurotransmitters?
- Only one neurotransmitter (Dale’s principle)
- Co-transmitters: two or more transmitters released from one nerve terminal
- Nomenclature (-ergic): cholinergic, noradrenergic, GABAergic, etc.
How are different particular transmitter systems defined?
By molecule, synthetic machinery, packaging, reuptake/degradation, and action
What are the 3 study criteria for establishing a neurotransmitter?
1) Synthesis and storage in presynaptic neuron
2) Released by presynaptic axon terminal
3) When applied, mimics postsynaptic cell response produced by release of neurotransmitter from the presynaptic neuron
What are 3 ways we study neurotransmitter systems?
1) Localizing transmitters and transmitter-synthesizing enzymes
2) In situ hybridization: localize synthesis of protein or peptide to a cell to detect mRNA
3) Immunocytochemistry: localize molecules to cells
What is the qualifying condition for studying synaptic mimicry?
Molecules evokes same response as neurotransmitters
What is microiontophoresis?
technique in which drugs can be ejected in very small amounts to assess postsynaptic actions
What are microelectrodes?
measures effects on membrane potential
What receptors are used in molecular analysis?
1) Transmitter-gated ion channels (ionotropic receptors)
- GABA (a) receptors
- 4-5 subunits, each made with various combos of subunit polypeptides
2) G-protein-coupled receptors (metabotropic receptors)
- GABA (b) receptors
- 7-transmembrane signaling molecules
What was the first identified neurotransmitter? Where is it typically found?
ACh (Acetylcholine) - vertebrate neuromuscular junctions
What happens in Cholinergic Neurons?
ACh synthesis and degradation
What enzyme is needed for ACh synthesis?
ChAT enzyme (Choline acetyltransferase)
What enzyme mediates ACh degradation?
acetylcholinesterase (AChE)
What are catecholaminergic neurons involved in?
movement, mood, attention, and visceral function
What is the precursor for dopamine, norepinephrine, epinephrine?
Tyrosine! They all contain catechol group
What enzymes are involved in making catecholamines?
Tyrosine hydroxylase, Dopa decarboxylase, Dopamine Beta-hydroxylase, phentolamine N-methyltransferase
What are serotonergic neurons derived from?
Tryptophan
What do serotonergic neurons regulate?
mood, emotional behavior, sleep
What can people take to help with serotonergic neurons?
SSRIs - Selective serotonin reuptake inhibitors
How is serotonin made?
2 steps from tryptophan with tryptophan hydroxylase and 5-HTP decarboxylase
What are examples of amine acidergic neurons?
Glutamate - major excitatory CNS neurotransmitter
CABA - major inhibitory CNS neurotransmitter
Glycine
What is glutamic acid decarboxylase (GAD)?
Key enzyme in GABA synthesis & good marker for GABAergic neurons
Why are GABAergic neurons important?
major source of synaptic inhibition in the CNS
What transporters are needed to load GABA and Glutamate into synaptic vesicles?
Vesicular GABA transporter (vGAT) and Vesicular glutamate transporter (vGlut)
What are examples of Ach receptors? What goes in and comes out in each?
Nicotinic receptor = + nicotine, - curare
Muscarinic receptor = + muscarine, - atropine
Both have + ACh in
What are examples of glutamate receptors? What are their respective agonists?
AMPA receptor: AMPA
NMDA receptor: NMDA
Kainate receptor: Kainate
What are the benefits of neurotransmitter-gated ion channels?
- Fast synaptic transmission
- Can turn chemical signal into electrical signal
- Ion selective
What is the basic structure of transmitter-gated channels?
Tetramer: 4 protein subunits form a pore
Pentamer: 5 protein subunits form a pore
What are AMPA receptors permeable to?
Na+ and K+
What are NMDA receptors permeable to?
Na+ and K+ and Ca++
How does the voltage-dependent NMDA channels work?
- Require glutamate binding and membrane depolarization to open channel
- Blocked by Mg++ ions at negative resting membrane potentials
- Removal of Mg++ block happens when membrane depolarizes
What does GABA-gated mediate?
Most synaptic inhibition in CNS
What do glycine-gated channels mediate?
non-GABA synaptic inhibition
What do amino acid-gated channels bind?
ethanol, benzodiazepines, barbiturates
What are other neurotransmitter systems?
endocannabinoids, retrograde messengers
- act on presynaptic g-protein coupled receptor cannabinoid receptors
What are the basic structures of g-protein couples receptors (GPCRs)?
Single polypeptide with 7 membrane-spanning alpha-helices
What are the 3 steps in transmission?
- Binding of the neurotransmitter to the receptor protein
- Activation of G-proteins
- Activation of Effector systems
What are the inactive g-protein subunits?
alpha bound to GDP, beta, gamma
When is GPCR active?
G-protein complex activated by receptor and exchanges GDP for GTP on G-alpha
How does GPCR activate, inactivate, and start over?
Alpha dissociates from beta-gamma and GDP swaps with GTP
G-alpha is inactivated by hydrolysis of GTP to GDP
Alpha and beta-gamma recombine to start over
What is the shortcut pathway for GPCR?
From receptor to G-protein to ion channel
- super fast and localized
What is the second messenger cascade pathway?
g protein couples with neurotransmitter with downstream enzyme activation
How does push-pull signaling work?
- different g-proteins stimulate or inhibit adenylyl cyclase)
- Gi : adenylyl cyclase inhibitory G-alpha protein
- Gs: adenylyl cyclase stimulatory G-alpha protein
Explain the IP3 and DAG signaling cascade.
1) G-protein activation of phospholipase C (PLC)
2) Lipase that hydrolzes phosphatidylinositol 4, 5-bisphospahete (PIP2) to make DAG and IP3
- IP3 binding to IP3 receptors at the ER to release calcium stores
- DAG helps activate protein kinase C
3) Activated different effectors
What’s the benefit of GPCR signaling cascades?
Powerful signal amplification
What is a common regulator mechanism of target proteins?
Phosphorylation and dephosphorylation
- changes conformation and biological activity
What is the difference between divergence and convergence?
Divergence: one transmitter activates more than one receptor subtype
Convergence: different transmitters converge to affect the same effector system
Which creates a greater postsynaptic response: divergence or convergence?
divergence
