Test 2: lecture 20-21 Flashcards
what are the most common neurotransmitters
glutamate, gaba, glycine
gluatamte is the major — neurotransmitter
excitatory (allows + into the cell → depolarization)
what are the three major classes of ionotropic glutamate receptors
NMDA
Kainate
AMPA
all ionotropic glutamate receptors are — channels
cation (allow + through, let K out and Na into the cell)
are excitatory- will cause depolarization of the cell
ketamine will block
NMDA ionotropic glutamate receptor
will stop depolarization (calm it down)
too much glutamate will do what to neurons
cause cell death!
how can glutamate lead to neurotoxicity and cell death
glutamate allows Na into a cell and K out, if too active the increase in Na will cause H20 to come into cell and cause swelling → cell lysis
can also cause delayed apoptosis
how is glutamate removed from the synapse
reuptake by ecitatory amion acid transporters (EAATS)
glial cells will also reuptake glutamate, turns it into glytamine and brings it back to presynaptic neuron for recycling
Excitatory Amino Acid Transporters (EAATs) are powered by —
electrochemical gradient (Na/K)
glutamate will cause Na into the synapse, K into the cell
will pull glutamate back into presynaptic neuron for recycling
how does ischemia effect NMDA activation
decreased blood flow= loss of Na/K pump= loss of membrane potention in the synapse
no potential means glutamate released will not reuptake by EAATs- this leads to prolonged NMDA activation → too much Na into the cell → swelling → cell death
domoic acid
toxin in marine algae
agonist for kainate receptor (type of ionotropic glutamate receptor)
leads to headache, confusion, muscle weakness and coordination deficits
the BIRDS
— is the major inhibitor neurotransmitter in CNS. and is used for inhibitory control of —
GABA
Important in inhibitory control of interneurons
GABA is made from
glutamate
glutamic acid decarboxylase (GAD)
neuron can not release both GABA and glutamate= one or the other
reuptake of GABA
same as glutamate
by GABA specific EAAT and glial cells
two types of GABA receptors
GABA A receptors are —
Cl- channels
allow Cl into the cell= inhibitory = hyperpolarization
GABA B receptors are —
G protein coupled
are connected to K+ channels (move K+ out of cell) to cause membrane hyperpolarization
inhibitory
benzos bind to what receptors and will do what?
bind to GABA A receptors
make it easier to channel to open= increases Cl- into the cell = inhibitory/ hyperpolarization of the cell
benzodiazepam (valium), alprazolam (xanax)
barbiturates bind to what receptors and will do what?
bind to GABA A receptors
channels stay open longer= increases Cl- into the cell = inhibitory/ hyperpolarization of the cell
barbiturate= phenobarbital
what are some barbiturates?
sodium amytal, pentobarbital, phenobarbital
what are barbiturates used for in vet med
sodium amytal, pentobarbital, phenobarbital
used for sedation, anesthesia, and seizure control depending on the duration of action by the drugs.
causes respiratory depression in high dose = euthanasia
barbiturates bind to GABA A receptors and make them open longer allowing more Cl- into cell → inhibitory
what are some bad symptoms of barbiturate use
can cause confusion, imparied judgment and slow reflexes
lethal at high dose→respiratory depression
high tolerance
bad withdrawal
easily and commonly abused
sodium amytal, pentobarbital, phenobarbital - used for sedation, anesthesia, and seizure control in animals
binds to GABA A receptors and make them stay open longer= inhibitory
what are some Benzodiazepines
diazepam (Valium®), alprazolam (Xanax®).
what are benzos used for
Short-acting BDZs used primarily as anxiolytics.
Long-lasting BDZs used as anxiolytics, muscle relaxants, anti-convulsants.
diazepam (Valium®), alprazolam (Xanax®).
bind to GABA A, and increased probablity of opening = inhibitory
glycine is an — neurotransmitter
inhibitory
where can you find glycine receptors
medulla and spinal cord inhibitory interneurons
what will glycine do
will bind to ionotropic receptors and will open Cl channels
allows Cl- into the cell→ inhibitory
strychnine
acts as competitive antagonist of glycine
plant from asia
if you have strychnine, you need more GABA to get to the same response
how are peptide transmitter made
two main classes of NT vesicles
large dense core vesicles → peptide transmitters
small synaptic vesicles → nonpeptide transmitters
how are large dense core vesicles made vs small synaptic vesicles
large: made in soma of neuron and transported down axon to nerve terminal
small: made “on site” neurotransmittings already in the nerve terminal are packaged into vesicles
if a nerve contains a classic neurotansmitter, can it also have peptide neurtransmitters?
yes
usually only 1 classical NT per nerve, but can have a bunch of peptide NT
peptide transmitters typically acts via — receptors. Generally modulate ion channels activity — via G-proteins.
G-protein coupled
indirectly
often slow transmission, with longer range response (can travel to new synapse), and longer lasting
what does it mean when peptide transmitters have longer range effect
they are released by neuron, but can float away to other synapase and cause signal there
usually slow transmission but responses generally last longer
how does peptide NT become deactivated
peptidases will eat peptide NT into smaller inactive fragments
what spinal tract carries pain to brain
spinothalamic tract
responds to heat, cold, mechanical and inflammation
— respond to sharp, prickling, well localized and brief pain
Aδ
fast conduction
myelinated
— nerves respond to dull ache, diffuse, long lasting pain
C
unmyelinated
slow conduction
nociceptors use — as transmitters to secondary neuron
glutamate and substance P
C fibers release —
Aδ fibers release —
C: glutamate and substance P
Aδ: glutamate only
C fibers will release — for small/mild stimuli
glutamate
C fibers release — for stronger stimuli and may signal persistent burning pain
substance P
C fibers: dull, diffuse, longer lasting pain, slower non myelinated
substance P is degraded by
peptidases
* Neutral endopeptidase (NEP)
* Angiotensin converting enzyme (ACE)
P substance binds to what type of receptors
neurokinin (tachykinin) receptors
NK1-3 maybe 4
mostly to NK1
all are GPCR that are linked to PLC activation (IP3 and DAG as second messengers).
NK1 receptors prefer to bind to —
substance P
neurokinin (tachykinin) receptor
where can you find substance P
skin- pain receptor
cardio: arterioles: cause low BP
respiratory: bronchoconstriction (asthma?)
GI tract: contracts GI
inflammatory: role in immune response, helps with migration of inflammatory cells
what does substance P do in the brain
Possible roles involve mood (depression), anxiety, control of respiration, nausea, and emesis
three opioid peptide families
endorphins
enkephalins
dynorphins
what are the three main families of opiate receptors
μ (mu)
κ (kappa)
δ (delta)
µ and κ receptors associated with analgesia.
δ receptor not as important in analgesic effects of opiates May be important for the euphoric effects of these drugs.
how do opioids effect pain
opioids (enkephalin, endorphins, dynorphins) are released from local inhibitory neurons
prevents release of NT(substance P and glutamate) from primary afferent nociceptors (C fibers)
what will opioids do to brain
activated dopamine in brain cause sensation of pleasure, and mediate asaptations to stress and extreme pain
how does nitric oxide get into cell
very small can just get into cells
very reactive radical, with short half life
Nitric oxide likes to bind to
heme
will bind even better then oxygen
what is a nitric oxide receptor and what happens when it bind
NO likes to bind to heme
will cause activation of soluble guanylyl cyclase which leads to ↑cGMP
cGMP will act as second messenger to:
* stimulate protein kinase G
* alter response of some ion receptors
* inhibit cAMP
how does nitric oxide gas in the brain work
enters postsynaptic neuron and causes the formation of more NO
NO will move retroactivly into presynaptic neurons to cause release of cGMP
NO acts on blood vessels as
endothelium derived relaxing factor (EDRF)
causes vasodilation and drop in blood pressure
