test 1: lecture 4 and 5 Flashcards
___ neuroanatomical structure that permits communication between a neuron and its target cell.
synapse
____ is the physical “gap” between neuron and target organ
synaptic cleft
axodendritic
axiosomatic synapse
axoaxonix
neurotransmitters are stored in ___
vesicles
three reasons to use vesicles to store neurotransmitters
quantal release (release entire payload into the synaptic cleft)
protect NT from degradation
storage- many NT are recycled
how does AP influence voltage gated N-type Calcium channels near synapse?
depolarization (+ charge) will cause Ca+ channels to open and Calcium will flood into the axon
How do NT get into synaptic vesicles
proton pump pushes H into vesicle
transmitter transporters will use the energy of returning H to the outside of the vesicle to bring NT into the vesicle
___ causes the release of vesicle from cytoskeleton
voltage gated Ca open
Calcium floods into cell
calcium-dependent phosphorylation of synapsin (Ca2+/calmodulin kinase)
calcium binds with synapsin and synapsin lets go
SNARES
Soluble N-ethylmaleimide-sensitive fusion protein attachment receptor
Vesicular (v-SNARE) vs Terminal (t-SNARE)
help vesicle bind to plasma membrane
2 types of V-snares
synaptobrevin
synaptotagmin
two types of t-SNARES
syntaxin
SNAP-25
___ regulates the assembly of SNAREs that tether the vesicle to the presynaptic membrane
SNAP-25 (a t SNARE)
___ is a Ca2+ sensor and catalyzes membrane fusion and NT unloading
Synaptotagmin
tetanus toxin damages what SNARE?
synaptobrevin (v-SNARE)
has to do with SNAP-25 (a t-SNARE) binding the vesicle to syntaxin(t-SNARE)
what toxin damages t-SNARES
botulinum
C1→ syntaxin and SNAP 25
A and E → SNAP-25
what SNARE will botulinum B,D,F,G and tenatus attack?
synaptobrevin (v-SNARE
C. botulinum bacterium grows in the intestinal tract and produces toxins. This happens most often in foals and is also called “___” Human correlate can happen by feeding honey to infants (< 1 years old).
shaker foal syndrome.
INGESTION OF PREFORMED TOXIN: Occurs when animals ingest feed that has been contaminated with ___ toxin, such as hay or silage that has been improperly produced or stored, or that has been contaminated by an animal that has died of botulism. This form can affect animals of any age
botulinum
where are ion channels found in mammalian CNS
–Vestibular nucleus
–Nucleus of trigeminal nerve
–Inferior olivary nucleus
(rare)
ion channels are formed by ___-
connexins
neuronal gap junctions
direct connection of one cell to another that allows ions to flow (share electrical current from cell to cell)
rare
formed by connexins
allow synchronous firing (fire one- fire them all)
Gap junctions allow for rapid ___ stimulation.
excitatory
can fire one and it will fire all that are directly connected
•Used to respond with high frequency (µsec) in nerve cells.
Stay open for seconds to minutes.
how is electrical current shared between cells
neuronal gap junctions
compare electrical and chemical synapses
what kind of synapse can be bidirectional?
electrical (neuronal gap junctions)
which synapse is wider electrical or chemical?
chemical
(synaptic cleft can be 30-50nm apart)
electrical (2-3 nm very small)
two types of Neurotransmitter receptors
ionotropic
metabotropic
if an ion channel is inhibitory what will happen
cell becomes more negative (hyperpolarization)
K+ will leave or Cl- will enter
if an ion channel is excitatory what will happen?
cell will become more positive (depolarization)
Na+ or Ca2+ will enter cell
ligand gated ion channels
type of neurotransmitter receptor
ionotropic receptor
ion binds and opens channel
___ is direct modulation of neuron excitability
ionotropic receptor
(ligand gated ion channel)
how do ionotropic receptors work?
neurotransmitter binds
channel opens
ions can flow in or out based on excitatory or inhibitory
___ are G protein coupled receptors
metabotropic
how does metabotropic receptor work?
neurotransmitter binds to receptor, this triggers change in G protein
alpha subunit will go off and cause secondary messangers
gamma and beta subunit will go off and cause downstream regulation of ion channels
___ will indirectly modulate neuron excitability by downstream regulation of ion channels
metabotropic receptors (G protein linked)
autoreceptors
•On presynaptic terminals either ionotopic or metabotropic
•Regulates transmitter release,
INHIBITS FURTHER NT RELEASE
•Can be a different subtype compared to postsynaptic receptors
POTENTIAL FOR SPECIFIC DRUGS TO CONTROL NT RELEASE
criteria for neurotransmitter
in terminal
Ca2+ dependent release
subject to inactivation
synaptic mimicry
receptors exist on postsynaptic cell
what is the most common type of neurotransmitter
amino acid NT
90% of synapses involve what 4 amino acid transmitters?
glutamate, aspartate, GABA or glycine
what amino acids NT are excitatory?
Glutamate, Asparate
what amino acid NT are inhibitory
GABA and glycine
(make cell more negative)
what kind of receptors do amino acid NT use?
Most work through ionotropic (ion channel) receptors.
Some use metabotropic receptors (i.e. linked to second messengers such as IP3 or cAMP).
how are amino acid NT inactivated
rapid re-uptake by energy dependent channels that will place amino acid into vesicles or into pool of amino acids
glial cells will also reuptake AA
the major excitatory NT is ___
glutatmate
3 types of ionotropic receptors for glutamate
- NMDA (N-methyl-D-aspartate)
- AMPA
- Kainate
The ___ receptor is of great interest because it seems to be heavily involved in learning and memory.
ionotropic NMDA
glutamate receptor (excitatory)
___ is the major inhibitory NT in the CNS
GABA
(γ-aminobutyric acid)
___ is important in inhibitory control of interneurons
GABA
how to make GABA
if a cell has glutamic acid decarboxylase (GAD) what amino acid NT does it use?
GABA
two types of GABA receptors
A: ion channel: Allow Cl- ions into neuron resulting in membrane _hyper_polarization
B: G-protein coupled, several subtypes cloned- Connected to K+ channels to cause membrane _hyper_polarization
GABA is an inhibitory NT
Increasing overall ___ of CNS is useful for sedation, anesthesia, anxiolytics, and seizure control
inhibition
ketamine blocks ___ receptor for ___
NMDA
receptor for glutamate which is excitatory
blocking this will have inhibitory effect
Benzo and barbituates act to enhance what receptors ___
GABAa
receptor for GABA which allows Cl- into the cell causing hyperpolarization or inhibitory effect
how to make acetylcholine
how does acetylcholine work as NT?
how is acetylcholine NT inactivated
there is acetylcholinesterase on the postsynaptic cell that breaks acetylcholine into acetate and choline
choline can be reabsorbed and used to make more acetylcholine
can acetylcholine released into the synaptic cleft be reused?
no they are broken down into choline and acetate, the cell has to make new ones every time
but choline can be reabsorbed and used to make more acetylcholine
what are some CNS functions of acetylcholine
Behavioral Arousal
Attention
REM sleep
Memory
Learning
Aggression
Grand Mal Seizures
Sensory Perception
Energy Conservation
Mood
Motor Coordination
___ is a prominent neurotransmitter of the Autonomic Nervous System
Acetylcholine
neuromuscular junctions use ___ as a NT
acetylcholine
____ are irreversible inhibitors of acetylcholinesterase inhibitors
organophosphates
- Insecticides: malathion, acephate, diazinon.
- Poisonous gases: Sarin and Soman.
Myasthenia gravis is an autoimmune disease with decreasing numbers of ___ receptors at neuromuscular junction
nicotinic
how to treat myasthenia gravis
give short acting reversible AChE inhibitor such as edrophonium chloride
myasthenia gravis is when receptors for ACh (nicotinic receptors) are low or damaged by blocking enzyme that breaks down ACh it allows more ACh to attach to the ACh receptors that are there
tyrosine is the precursor to what type of monoamines?
catecholamines such as dopamine, norepinephrine and epinephrine
dopamine, norepinephrine and epinephrine are ___
catecholamines derived from tyrosine
type of monoamines
tryptophan gives rise to what type of monoamine?
indoleamines
serotonin and melatonin
serotonin and melatonin are __
type of indoleamines derived from tryptophan
type of monoamine
what is the precursor of histamine
histidine
what is the rate limiting step to make catecholamines?
how to make norephinephrine
tyrosine (tyrosine5 hydroxylase) → DOPA(aromaic amino acid decarboxylase)→ dopamine (dopamine-β-hydroxylase) →norephonephrine
how to make epinephrine
tyrosine (tyrosine5 hydroxylase) → DOPA(aromaic amino acid decarboxylase)→ dopamine (dopamine-β-hydroxylase) →norephonephrine (phenylethanolamine-N-methyl transferase) → epinephrine
compare catecholamine to (indoleamine) serotonin production
similar rate limiting step
same enzyme for 2nd step
compare breakdown of catecholamine and indoleamines
serotonin is an indoleamine
Monoamine Oxidase breakdown __
can break down both indoleamines(serotonin) and catecholamines(dopamine, norephinephrine, epinephrine)
•Serotonin, norepinephrine, and epinephrine mainly broken down by ___
MAO-A
Monoamine Oxidase
•Dopamine broken down equally by ___
both MAO-A and MAO-B
MAO is a mitochondrial enzyme and is NOT the mechanism for removal of monoamines from___
the synapse
how are catecholamine (such as dopamine) inactivated in the synaptic cleft?
rapid reuptake by specific transporters
how are catecholamine (such as norepinephrine) inactivated in the synaptic cleft?
rapid reuptake by specific transporters
how is serotonin inactivated?
what are two places dopamine NT are used in the brain?
ventral tegmental area
sustantial nigra
function of dopamine
- Hypothalamic regulation of hormones (anterior pituitary)
- Substantia nigra to basal ganglia play major role in movement.
- Midbrain projections to cortex & limbic system involved in schizophrenia, central “reward” pathway, working memory.
parkinson is the destruction of
dopaminergic neurons in the substantia nigra (which plays a major role in movement)
where is serotonin NT used in the body
- 90% present in the enterochromaffin cells of GI tract
- 8% in platelets
- 1-2% in CNS
function of norephinephrine
- A role in attention (vigilance).
- Involvement with control of feeding (stimulatory).
- Connection to mood (depression)
- Cell bodies of NE neurons reside in pons and medulla
- Locus coeruleus (LC), lateral tegmental area (LTA), and dorsal medullary (DM).
where in the CNS are serotonin NT?
raphe nuclei
serotonin function and location in the brain
how does prozac work?
blocks the reuptake of serotonin
(anti-anxiety medication)
