Exam 2: Acetylcholine Flashcards
neurons that use Ach are called
cholinergic
where are acetylcholine neuron cell bodies located
- basal forebrain
- striatum
- dorsal lateral pons (PPN, LTD)
involved in attention, memory, learning
- provides Ach to cerebral cortex (lobes of brain) and hippocampus
- made of many regions (nucleus basalis is main region)
cell bodies in basal forebrain but axons extend out
basal forebrain
striatum
cell bodies AND axons in striatum
movement
balance between dopamine and acetylcholine
dorsal lateral pons (PPN and LTD)
pons - part of brainstem
-cell bodies project to spinal nerves for movement, cerebellum, basal ganglia
balance and coordination, gait (walking)
what is acetylcholine important in
CNS (learning, memory, attention, motor movements) neuromuscular junctions (contract muscles, maintain posture) autonomic nervous system
branches of autonomic nervous system and how they relate to Ach
sympathetic - only preganglionic Ach
parasympathetic-pre and postganglionic Ach
Ach monitors if the body is in a state of arousal or stress
What is Acetylcholine formed from and what is it catalyzed/synthesized by?
formed from: choline and acetyl CoA
synthesized by: choline acetyltransferase (ChAT)
acetylcholine storage and release - how is it moved into vesicles
stored in vesicles at axon terminals
moved into vesicles by vesicular Ach transports (VAChT) embedded in vesicle memrbane
what are the VAChT blocked by
vesamicol
this reduces the amount of Ach released when the neurons fire
- if Ach cannot get packaged there s a decrease in Acetylcholine released in response to an action potental
what toxin inhibits Ach releas
botulism toxin
- prevents fusion of synaptic vesicles to the presynaptic membrane
- cannot release its contents - paralyzes the face
acetylcholine inactivation
- ALL Ach BROKEN DOWN
enzyme: acetylcholinesterase (AchE) breaks it down into choline and acetate
where is acetylcholinesterase found?
- in presynaptic cell (metabolizes excess Ach)
- on the membrane of postsynaptic cell (breaks Ach down after release after bound to receptor)
after acetylcholine inactivation what is transported back into the cell for reuse
choline
is there a reuptake transporter for Ach?
NO
drugs that block AChE prevent _____
inactivation of ACh which increases postsynaptic effects of the transmitter
how can drugs that block AChE be harmful
- can cause muscle paralysis or death (asphyxiation)
- depends on BBB permeability and whether it blocks AChE reversibly or irreversibly
- insecticides, sarin gas (SLUDGE)
- cardiac muscle has M2 receptors, stimulate parasympathetic system, dec HR, dec contraction strength and can kill someone (excess Ach, excess slwoing of heart and breathing)
SLUDGE
S: salivation/drooling L: lacrimation U: urination D: diarrhea G: GI distress E: vomiting, emesis
acetylcholine receptors
nicotinic and muscarinic
nicotinic receptors
ionotropic
- Ach binds, channel opens and Na or Ca enter cell, depolarizing it
- mediate fast excitatory responses in both CNS and PNS
nicotinic subunits
each receptor has 5 protein subunits (alpha, beta, gamma, delta, epsilon)
10 types of alpha, 4 types of beta
receptor in muscle cells have diff composition than ones in neurons
- muscles have lots of variety (2a1, B1, y, and delta or epsilon
- neurons have a7 - al a7 or a4b2(2a4, 3b2)
what are the two types of neuronal nicotinic receptors ((a4)2 and (b2)3)involved in … and where in brain?
learning, memory, cognition - targets of medications under development
- basal forebrain, caudate putamen, cerebellum, temporal lobe
distribution of nicotinic receptors in PNS vs CNS
PNS: neuromuscular junctions and ganglia of ANS
CNS: hippocampus and cerebral cortex, basal ganglia, ventral tegmental area and nucleus accumbens
3 states of nicotinic ionotropic receptors
closed-neurotransmitter not bound, channel closed
open-agonist is bound and pore opens
desensitized - pore is closed and cannot be opened by agonist binding while in this state (related to tolerance and reduced responding)
prolonged exposure to an agonist on a nicotinic receptor…
enhances the rate of conversion to the desensitized state
when is a desensitized receptor able to respond to an agonist again?
afte re-sensitization
what is a depolarization block
the resting potential of a membrane is lost
cell cannot be excited until agonist removed and membrane repolarized
example of a depolarization block
succinylcholine - muscle relaxer -resistant to breakdown by AChE - continually activates receptor and induces depolarization block of the muscle cell membrane potential never resets
muscarinic receptors
metabotropic
M1-M5
M1,3,5 - excitatory
M2,4 - inhibitory
which muscarinic receptor is highly implicated in addiction and pleasure
M5
- found on dopamine neurons in VTA
implicated in reward
