Exam I | Neurotransmitters and Synapses Flashcards
Describe the 5 steps of release of neurotransmitter from the pre-synaptic cell to the post-synaptic cell.
1) AP arrives at axon terminal of presynaptic cell
2) Voltage-gated Ca2+ channels open with depolarization, allowing influx of ions
3) Ca2+ binds regulatory proteins initiating exocytosis
4) Vesicles release NT into synaptic cleft
5) Molecules diffuse into and across cleft to bind post-synaptic receptors
5) Response in post-synaptic cell (depolarization or signaling sequence) is initiated
When Volatge-gated Ca2+ channels open, is the concentration of Ca2+ greater on the inside or outside?
outside
What happens in EPSP?
neurotransmitter passes postsynaptic cell membrane
What happens upon post-synaptic cell binding of a neurotransmitter?
- can inhibit or excite post-synaptic neuron (depending on the nature of receptors) by altering the membrane
- post-synaptic cell may respond to receptor binding by altering metabolism, secretion, or transcription
Does neurotransmitter activity depend more on the neurotransmitter type or the receptor characteristics?
receptor characteristics
Receptors on a post-synaptic cell can be what two things?
- ion channel
- G-protein cascade initiator
What 2 ways can neurotransmitter receptors initiate a response in the post-synaptic cell?
- directly or indirectly gating an ion channel (ligand-gated)
- initiating a 2nd messenger cascade
What 3 advantages does 2nd messenger cascade have over direct/indirect gating of an ion-channel?
- signal amplification
- greater regulation of pathway
- flexibility (diverse responses)
What is the receptor for GABA? What is the result of GABA binding?
- Receptor is a Cl2+ channel
- binding of GABA causes hyperpolarization and inhibition (IPSP)
What is G protein involved in?
second messenger signaling
What are two ways cell signaling pathways can be simplified?
- ionotropic (“fast”) synaptic potentials
- metabotropic (“slow”) synaptic potentials
Describe ionotropic synaptic potentials.
- fast. binding of nt causes immediate change in membrane potential
- direct or “almost” opening of a ligand-gated ion channel
Describe metabotropic synaptic potentials.
- slower, more persistent response than ionotropic
- involves 2nd messenger signaling (usually G-protein)
- membrane potential may change after intermediary reactions
What do nicotinic and amino acid neurotransmitters have in common?
they are ligand-gated (receptor is ionotropic)
What are the 4 ionotropic receptors (include the neurotransmitter that binds them)?
- nicotinic (Ach)
- NMDA &A (glutamate)
- receptor for GABA
- receptor for glycine
What is Ach short for?
acetyl-choline
What are the 5 metabotropic receptors (include the neurotransmitter that binds them)?
- muscarinic (Ach)
- alpha, beta (adrenaline)
- D1, D2, etc. (dopamine)
- 5-HTs, except for 5-HT3 (serotonin)
- membrane (peptides)
Is Ach binding to nicotinic receptors excitatory or inhibitory?
excitatory
Is GABA excitatory or inhibitory?
inhibitory
What neurotransmitters fall under the amine class?
- dopamine
- serotonin
- adrenaline
- histamine (not on chart)
What amines are subclassified as catecholamines? Why?
- adrenaline (epinephrine) histamine, norepinephrine, and dopamine
- they are synthesized by tyrosine
What neurotransmitters are classified as amino acids?
- GABA
- Glycine
- Glutamate
- and Aspartate (not on chart)
Distinguish an agonist from an antagonist.
- agonist is chemical that performs normal response
- antagonist is chemical that blocks normal response
Tryptophan hydroxylases synthesize what neurotransmitter?
serotonin
MAO stands for what?
Monoamine oxidase
What do MAO and COMT catabolize?
the amines (serotonin, dopamine, and adrenaline)
What is the descriptive name for Ach activity, and what class does Ach fall under?
cholinergic
What are the descriptive names for adrenaline, dopamine, and serotonin activity?
- adrenergic
- dopaminergic
- serotonergic
What are the descriptive names for glutamate, GABA, and glycine activity?
- glutamatergic
- GABAergic
- glycinergic
What are the receptors for Ach? Are they fast or slow?
- nicotinic (fast)
- muscarinic (slow)
What are the receptors for the amines? Are they fast or slow?
- adrenaline: alpha and beta,
- dopamine: D1, D2, etc.,
- serotonin: 5HTs, except 5HT3.
- all are slow
What are the receptors for the amino acids? Are they fast or slow?
- Glutamate: NMDA and AMPA
- GABA: GABA
- Glycine: no receptor
- all are fast
What are the enzymes that synthesize and catabolize Ach, respectively?
- choline acetyl-transferase (CHAT) synthesizes
- acetyl-cholinesterase (ACHE) catabolizes
CHAT stands for what?
choline acetyl-transferase
ACHE stands for what?
acetyl-cholinesterase
Ach receptor antagonists
- curare, alpha-bungarotoxin (nicotinic)
- atropine & scopolamine (muscarinic)
Adrenaline receptor antagonist
alpha or beta blockers, inhibitors
dopamine receptor antagonist
haloperidol, chlorpromazine
serotonin receptor antagonist
clozapine, etc. (for 5-HT2A)
glutamate receptor antagonist
ketamine, dextromethorpan
GABA receptor antagonist
block inhibition, have stimulant effects
glycine antagonists
none
What is the abbreviation for nicotinic acetylcholine receptors?
nAChR
What are the cholinergic receptors?
nicotinic & muscarinic
Nicotinic receptor importance
- receptors of neuromuscular junction
- first part of sympathetic and parasympathetic nervous system
What are the 3 types of nicotinic receptors?
- N: CNS
- G: ANS
- M: skeletal muscle
What are the AGONISTS of nicotinic receptors?
- nicotine
- choline
What are the antagonists of nicotinic receptors?
- snake venom alpha-bungarotoxin (neurotoxin)
- curare
Are nicotinic receptors ionotropic or metabotropic?
ionotropic
Muscarinic receptor
- finish parasympathetic NS
- broad distribution throughout CNS
- GI functions such as salivation, increasing stomach acid
Are muscarinic receptors isotropic or metabotropic?
metabotropic
What are the 5 muscarinic receptors, and where are they found?
- M1: (CNS, stomach)
- M2 (heart, brainstem)
- M3 (smooth muscle)
- M4 and M5 (basal nuclei)
Which muscarinic receptors inhibit?
M2 and 4
Which muscarinic receptors excite?
M1, M3, and M5
M2: what is it, where is it found, and what does it do?
- inhibitory muscarinic receptor
- found in heart
- decreases heart rate, force, and AV conduction
M3:, what is it, where is it found, and what does it do?
- excitatory muscarinic receptor
- found in smooth muscle and exocrine glands
- involved in glandular secretion and all smooth muscle contraction EXCEPT vasodilation
What classifies something as a catecholamine?
being derived from tyrosine
What are 4 aminergic neurotransmitters?
- adrenaline and dopamine (catecholamines)
- serotonin
- histamine
What are the adrenergic neurotransmitters?
epinephrine and norepinephrine
What do the adrenergic receptors bind to?
alpha or beta receptors
What are the 3 catecholamines?
- norepinephrine
- adrenaline (epinephrine)
- dopamine
What are neurocrines and give 2 examples?
- both hormone and nuerotransmitters
- epinephrine and norepinephrine
epinephrine and norepinephrine both fall under what two classes?
catecholamines and neurocrines
what are alpha and beta receptors critical to? Are they metabotropic or ionotropic?
- sympathetic (ANS) activation
- metabotropic
alpha 1 receptors
- cause sympathetic VASOCONSTRICTION of arterial smooth muscle
- cause relaxation of GI smooth muscle
alpha 2 receptors
largely inhibitory
beta 1 receptors
tend to upregulate cardiac function
beta 2 receptors
-cause VASODILATION of blood vessel
importance of dopamine (2 points to remember)
- involved in movement control, motivation, reward, and reinforcement
- many addictive substances work by affecting dopaminergic neurons
what does an autoreceptor do? Give an example
- regulates reuptake and catabolism of neurotransmitter
- dopamine re-uptake transporter
What are MAO-B and COMT enzymes?
catabolic enzymes that target all catecholamines
Describe what happens at the dopaminergic synapse (4 steps)
- AP arrives at synapse
- calcium-dependent exocytosis releases dopamine
- unbound dopamine is re-uptaken by presynapse
- that dopamine is then degraded/recycled by MAO-B COMT
What does SSRI stand for, and what does it do?
- selective serotonin reuptake inhibitor
- increases amount of serotonin at the synapse
What does SNpc stand for?
substantia nigra pars compacta (black area of brainstem)
What anomaly is associated with Parkinson’s symptoms?
loss of dopamine at the dopaminergic synapses of the substantia nigra pars compacta (SNpc)
schizophrenia is associated with what anomaly?
overactive dopamine
What are the 4 dopaminergic pathways?
1) mesocortical
2) tuberoinfundibular
3) mesolimbic
4) nigrostriatal
What dopaminergic pathway is most important for motor function, and where does it originate and end?
- nigrostriatal pathway
- extends from brainstem up to the striatum
What is the brain’s dopaminergic fundamental reward pathway?
Mesolimbic pathway
What dopaminergic pathway is involved with mood and social interactions? To where does it extend?
- mesocortical pathway
- extends into forebrain
what are the dopamine receptors?
D1-like
D2-like
What are the D1-like receptors? What do they do? Are they excitatory or inhibitory?
- include D1 and D5
- couple to G-alpha-olf or G-alpha-s and activate adenyl cyclase (AC)
- act to regulate Ca channels, also modulate NMDA receptors
- are excitatory
What are D2-like receptors? What do they do? Are they excitatory or inhibitory?
- include D2, D3, & D4
- coupled to G-alpha-i/o, which inhibits the AC-cAMP-PKA transduction pathway
- are inhibitory
What is the proper name for serotonin?
5-HT
What 3 areas is serotonin found in?
- GI tract (90%)
- CNS
- platelets
Where do serotonergic pathways originate?
raphe nuclei of brainstem
What are the functions of serotonin?
- regulates motility and secretion in GI tract
- act as a vasoconstrictor at sites of bleeding
- regulates mood, sleep, appetite, memory formation
- modulates activity of other neurotransmitters
How many receptors are there for serotonin? Are they ionotropic or metabotropic?
- there’s 12
- all are metabotropic except 5-HT3
What mediates serotonin re-uptake?
SERT transporter
What inhibits the SERT transporter?
- SSRI
- MDMA
- amphetamine
- cocaine
Insufficiency of serotonin can lead to what?
- neonate death
- OCD
- depression/anxiety
What is acetylcholinesterase? Where is it located?
- chops up and degrades acetylcholine in the synaptic cleft before it binds to receptors
- may or may not be located on the post-synaptic cell
What would an MAO inhibitor do in aminergic synapse?
- would cause aminergic to accumulate in the pre-synaptic cell
- resulting greater concentration within the cell would cause transporter to stop bringing in aminergic
Distinguish aminergic and cholinergic disposal at the synapse.
- cholinergics are not re-uptaken by the pre-synapse; only the debris caused by acetylcholinesterase, which cleaves/degrades Ach before it binds to receptors on post-synapse
- excess aminergics are re-uptaken and degraded by MAO and COMT
What are the 3 amino acid neurotransmitters? are they excitatory or inhibatory?
- aspartate, excitatory
- glutamate, excitatory
- glycine, inhibatory
What is the difference between AMPA and NMDA receptor?
- NMDA is voltage-gated and ligand-gated
- AMPA is only voltage gated (Na+ channels)
What is required for the activation of NMDA?
- binding of a ligand, usually glutamate and glycine (can be 2 glutamates)
- voltage-gating is dependent on Mg2+ or Zn2+ binding
What does NMDA stand for
N-methyl-D-aspartate
NMDA is involved in what processes?
learning, memory, and synaptic plasticity
What ions hyperpolarize the cell?
K+ and Cl2-
What is the difference between GABA A and GABA B receptors?
- GABA A is much more abundant, ionotropic (Cl2- channel)
- GABA B is metabotropic (G-protein receptor)
How is GABA recycled?
- by glial cells (astrocytes) that turn it into glutamine
- by the presynaptic cell
GABA A receptor
- hyperpolarizes as Cl2- enters cell
- has binding sites for sedatives (benzodiazepines and alcohol) and steroids, which enhance hyperpolarization,
Most antidepressants target what pathway?
catecholamine
List the major classes of antidepressants in general order of use.
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
- Atypical Antidepressants
- Tricyclic and Tetracyclic
- MAO inhibitors (MAOi)
What is the receptor for glutamate?
NMDA & AMPA
