Please enter something

Neurotransmission & Neurochemistry

question

What is a synapse?
answer

specialized junctions where neuronal axons contact another neuron or cell type
question

Type I synapse
answer

-excitatory -axodendritic -round presynaptic vesicles -presynaptic specialization -large active zone -wide cleft -large postsynaptic density
question

Type II synapse
answer

-inhibitory -axoaxonic -flat presynaptic vesicles -few presynaptic specializations -small active zone -narrow cleft -non-uniform postsynaptic density
question

SNARE proteins
answer

expressed in membranes of neurotransmitter vesicles and axon terminals; facilitate docking
question

synaptotagmine
answer

Ca2+ sensor protein in membrane of neurotransmitter vesicles
question

synaptobrevin
answer

allows neurotransmitter vesicle to bind with cell membrane; interacts with syntaxin & SNAP-25
question

G-alpha-s subunit
answer

activates adenylyl cyclase–> more cAMP–> more active PKA
question

G-alpha-i/o subunit
answer

inhibits adenylyl cyclase–> less cAMP–> less PKA
question

G-alpha-q subunit
answer

stimulates phospholipase C-beta–> breaks PIP2 into IP3 + DAG
question

4 characteristics to be a neurotransmitter
answer

1. Produced & stored in vesicles in presynaptic neuron 2. Released in response to presynaptic depolarization; Ca-dependent 3. High-affinity receptors on post-synaptic cell 4. Mechanism to terminate activation
question

3 mechanisms to terminate neurotransmitter action
answer

1. Diffusion away from receptor 2. Enzymatic degradation 3. Re-uptake
question

choline acetyltransferase (ChAT)
answer

synthesizes acetylcholine from choline + acetyl CoA in presynaptic cell
question

vesicular acetylcholine transporter
answer

transports ACh into vesicle for storage in presynaptic cell
question

acetylcholine esterase (AChE)
answer

hydrolyzes acetylcholine–> choline + acetic acid *FASTEST enzyme in the body!
question

choline transporter
answer

brings choline back into presynaptic cell so it can be used for synthesis of ACh
question

agonists of muscarinic receptors
answer

acetylcholine, muscarine
question

subtypes of muscarinic receptors
subtypes of muscarinic receptors
answer

*M1, M3, M5–> Gq –> PLC–> more Ca *M2, M4–> Gi–> inhibit adenylyl cyclase
question

agonists of nicotinic receptors
answer

acetylcholine, nicotine
question

alpha-bungarotoxin
answer

irreversibly binds & inhibits (competitive antagonist) activation of muscle nicotinic ACh receptors & alpha-7 nicotinic ACh receptors
question

curare
answer

inhibits ALL nicotinic ACh receptors (competitive antagonist)
question

nicotinic receptors
answer

ionotropic: non-selective cation channels 5 subunits, doughnut shape 2nd transmembrane domain of each subunit lines ion channel agonist binds N-terminal domain of alpha subunit
question

What is the end plate potential (EPP)?
answer

Depolarization of skeletal muscle fibers caused by neurotrasmitters binding to post-synaptic receptors -always a multiple of mEPPs–> need MULTIPLE vesicles to release NT
question

What is the miniature end plate potential (mEPP)?
answer

Depolarization of a skeletal muscle fiber resulting from the ACh released from ONE vesicle – happens spontaneously, even when there’s no AP in pre-synaptic neuron
question

Myasthenia gravis
answer

Organ-specific autoimmune disorder Usually auto-antibodies against muscle nAChRs Sometimes antibodies against MusK (stabilizes nAChR expression at NM junction) -muscle weakness starts at eyes–> moves down -gets worse with activity
question

Pyridostigmine
answer

Reversible inhibitor of acetylcholinesterase–> increases lifetime of ACh in synaptic cleft Treat myasthenia gravis
question

Lambert-Easton Myasthenic Syndrome (LEMS)
answer

Auto-antibodies against Ca channels in pre-synaptic motor neurons -muscle weakness starts at extremities–> moves up -gets better with activity
question

Organophosphorus pesticide poisoning: Cholinergic crisis
answer

irreversible inhibition of acetylcholinesterase–> over-stimulation of muscarinic & nicotinic receptors Muscarinic syndrome: miosis (pupil contriction), profuse secretions, bradycardia, bronchoconstriction, hypotension, diarrhea Nicotinic syndrome: tachycardia, muscle weakness CNS: anxiety, confusion, tremors, seizures, cardiorespiratory paralysis
question

What is the important structural difference between nAChR subunits and ionotropic glutamate subunits?
answer

nAChR subunits each have 4 transmembrane domains vs Ionotropic glutamate receptor subunits: 2nd “transmembrane” domain loops back inside, doesn’t actually cross the cytoplasmic membrane
question

3 functional classes of ionotropic glutamate receptors
answer

NMDA AMPA Kainate *All have 5 subunits, non-selective cation channels
question

What is the major mechanism for terminating the action of GLUTAMATE in the synaptic cleft?
answer

Glial cells take up GLUTAMATE–> Glutamine synthase makes GLUTAMINE–> releases back to pre-synaptic cells
question

How do Class II metabotropic glutamate receptors (mGluR2 & 3) lead to inhibition of the post-synaptic cell?
answer

These receptors are coupled to a Gi alpha subunit: bind Glu–>reduce adenylyl cyclase activity–>reduce PKA activity–> INCREASE K channel activity–> K flows out of cell–> HYPERPOLARIZATION = inhibition
question

How do Class I metabotropic glutamate receptors (mGluR1 & 5) lead to plasticity in the post-synaptic cell?
answer

These receptors are coupled to Gq alpha subunits: bind Glu–>activate PLC–>increase DAG & IP3–>increase PKC & [Ca]–>modify translation and transcription = PLASTICITY
question

How can metabotropic glutamate receptors lead to pre-synaptic inhibition of glutamate release?
answer

These receptors are bound to Gi alpha subunits: bind Glu–>inhibit adenylyl cyclase–>inhibit Ca influx via Ca channels–>prevent depolarization = INHIBITION
question

What determines the calcium permeability of AMPA receptors?
answer

RNA editing of the GluR2 subunit: if arginine gets substituted for glutamine at a certain position, the channel will be IMPERMEABLE to Ca
question

What makes NMDA unique among ALL neurotransmitter receptors?
answer

To be activated, it requires simultaneous binding of: -primary agonist (glutamate, aspartate, or NMDA) -co-agonist (glycine, serine)
question

What is the role of MAGNESIUM in NMDA receptor signaling?
answer

Extracellular concentration exerts a voltage-dependent block of the channel
question

How is the Mg block of NMDA receptors removed?
answer

Membrane depolarization; usually accomplished by activation of AMPA receptors
question

Kynurenic acid
answer

competitive antagonist at the glycine site on NMDA receptors
question

Non-competitive antagonists of NMDA receptors
answer

1. PCP (phencyclidine, drug of addiction) 2. Ketamine (anesthetic) 3. Ifenprodil 4. Memantine (Alzheimer’s) 5. Lead (Pb2+)
question

How do extrasynaptic NMDA receptors differ from synaptic NMDA receptors?
How do extrasynaptic NMDA receptors differ from synaptic NMDA receptors?
answer

Synaptic–> turn on CREB pathways–> cell survival–> plasticity Extrasynaptic–> shut off CREB pathways–> cell death
question

Memantine
answer

Non-competitive antagonist of EXTRASYNAPTIC NMDA receptors; prevent neuronal death in late-stage Alzheimer’s *NOT for early disease b/c also blocks nicotinic receptors
question

What are the 2 ways that GABA is re-uptaken from the synaptic cleft?
answer

1. Re-uptake by pre-synaptic neuron 2. Re-uptake by glial cells–> convert to Gln–> release back to pre-synaptic neuron
question

Type of cell where GABA trasmission is mostly used
answer

Interneurons– control activity of excitatory pathways in the brain
question

Barbiturates
answer

Increase the DURATION of GABA-induced channel activation–> inhibition of other neurons *Anti-convulsant
question

Benzodiazepines
answer

increase the FREQUENCY of GABA-induced channel activation–> inhibition of other neurons *Anti-convulsant
question

Antagonists of GABA receptors
answer

Cause convulsions by relieving inhibition of excitatory neurons – Bicuculline – Picrotoxin – Dieldrin (organochlorine pesticide)
question

Ionotropic GABA receptors
answer

GABA- A and C (C is only expressed in retina) Permeable to Cl- Just like nicotinic ACh receptors: 5 subunits with 4 transmembrane domains each, 2nd domain lines channel
question

When is GABA signaling excitatory instead of inhibitory?
answer

Developing brain: predominant expression of NKCC1–> high resting intracellular [Cl-]
question

Why is GABA signaling inhibitory in the adult brain?
answer

KCC2 expression prevails over NKCC1–> low resting intracellular [Cl-]–> GABA stimulation makes Cl- flow in–> hyperpolarization
question

Metabotropic GABA receptors
answer

GABA-B Coupled to Gi proteins–> inhibits adenylyl cyclase Beta-gamma dimer inactivates voltage-gated Ca channels, activates voltage-gated K channels
question

Baclofen
answer

Agonist of GABA-B receptors Treat muscle spasms
question

Major inhibitory neurotransmitter in the spinal cord
answer

Glycine
question

Inhibitory interneurons in spinal cord, feedback inhibition loop with motor neurons; use glycine as neurotransmitter
answer

Renshaw cells
question

Serine hydroxymethyltransferase
answer

Serine–>Glycine in presynaptic terminal Needs folate as co-factor
question

Hyperekplexia
answer

Exaggerated startle response to acoustic & tactile stimuli Caused by mutation in glycine receptor alpha subunit
question

Glycine receptors
answer

Ionotropic ONLY Permeable to Cl-
question

Strychnine
answer

Inhibits glycine receptors–> excessive muscle contraction Rat poison
question

4 steps in catecholamine synthesis
answer

1. Hydroxylation: tyrosine–> DOPA 2. Decarboxylation–> dopamine 3. Hydroxylation–> norepinephrine 4. Methylation–> epinephrine
question

What is the rate-limiting step in catecholamine synthesis?
answer

Tyrosine hydroxylase: tyrosine–> DOPA
question

4 co-factors for tyrosine hydroxylase
answer

1. Fe2+ 2. Oxygen 3. Biopterin 4. NADPH
question

2 ways to increase activity of tyrosine hydroxylase
answer

1. Phosphorylation of TH; mediated by increased intracellular cAMP 2. Phosphorylation of CREB (long-term, only after prolonged neuronal activation)
question

2 feedback inhibitors of tyrosine hydroxylase
answer

Norepinephrine Dopamine (via autoreceptors)
question

Only enzyme in catecholamine synthesis that’s located inside the NT vesicle
answer

Dopamine beta-hydroxylase (dopamine–>NE)
question

PNMT enzyme is expressed mostly in what tissue?
answer

Adrenal chromaffin granules (NE–>epi) A few neurons also do this
question

Controls uptake of monoamines into synaptic vesicles
answer

VNMTs (vesicular monoamine transporters)
question

Primary breakdown product of dopamine; low levels in CSF are diagnostic of___
Primary breakdown product of dopamine; low levels in CSF are diagnostic of___
answer

Homovanillic acid (HVA) Disorders of the basal ganglia
question

2 enzymes involved in breakdown of catecholamines
answer

Monoamine oxidase (MAO) Catecholamine-O-Methyl transferase (COMPT)
question

Primary breakdown product of norepinephrine; high levels in blood are diagnostic for ___
Primary breakdown product of norepinephrine; high levels in blood are diagnostic for ___
answer

Vanillylmandelic acid (VMA) Pheochromocytoma
question

Major means of terminating dopamine synaptic activity
answer

Reuptake into presynaptic cells by dopamine transporters
question

4 similarities between catecholamine and serotonin synthesis
answer

1. Dietary source 2. Hydroxylated by rate-limiting enzyme 3. Decarboxylated by AAD 4. Degraded by oxidation by MAO
question

Driving force for NT reuptake via SLC6 transporters
answer

Na (co-transport) or K (counter-transport) gradient
question

Alpha adrenergic receptors
answer

Excitatory Increase calcium or reduce cAMP
question

Beta adrenergic receptors
answer

Inhibitory Increase cAMP
question

D1 receptors
answer

for dopamine increase cAMP not autoreceptors
question

D2 receptors
answer

for dopamine decrease cAMP can be autoreceptors targets for antipsychotics
question

2 norepinephrine pathways in the brain
answer

1. locus coeruleus–> cortex reticular formation–> NTS 2. spinal cord
question

2 dopaminergic pathways in the brain
answer

1. Nigrostriatal (substantia nigra–> striatum) 2. Mesolimbic (VTA–> frontal cortex & nucleus accumbens)
question

serotonergic pathways in the brain
answer

more diffuse that catecholaminergic pathways cell bodies in Raphe nuclei–> project to multiple areas throughout brain *Sleep, wakefulness, mood
question

Regulation of neuropeptide expression is largely ______.
answer

transcriptional (transcription factors, e.g. CREB, bind to response elements, turn transcription on/off)