lecture 12 LOs Flashcards
where is ACh a key NT
peripheral and central nervous systems
what does ACh do in the peripheral nervous system
used at all neuromuscular junctions and parasympathetic nervous systems
what does ACh do in the central nervous system
multiple cell body regions enervate cortical/subcortical regions and the ACh interneurons in the striatum
what is ACh made from
choline and acetyl coenzyme A
what are the components of ACh catalyzed by
choline and acetyl coenzyme A are catalyzed by choline acetyltransferase (ChAT)
where is ChAT found
only in neurons that use Ach
what is the rate of ACh synthesis controlled by
avaiability of precursors
rate of cell firing
are there selective inhibitors for ChAT
none have been found
what packages ACh into vesicles
vesicular ACh transporters (VAChT)
what does vesamicol do
blocks VAChT (what packages ACh into vesicles) and reduces ACh levels
what does black widow spider venom do
causes massive ACh release in the PNS
cholinergic over activity causes muscle pain, tremors, nausea, vomiting, salivation, copius sweating
what does botulinium toxin do to ACh
inhibits its release selectively in nueromuscular joints
does ACh undergo direct reuptake
no
how are ACh levels controlled
by acetylcholinesterase (AChE)
what does AChE do
rapidly breaks down to choline and acetic acid
where is AChE found
on post synaptic membranes and in presynaptic cells that metabolize excess ACh
what happens to ACh after breakdown
most choline is taken back into the cholinergic nerve terminal by a choline transporter
what does hemicholinium-3 (HC-3) do
blocks choline transporters
reduces rate of ACh production
what is physostigmine used for
crosses the blood brain barrier
certain types of ACHE-inhibitors are used to offset some of the decline in Alzheimers
what is sarin and what does it do
very toxic nerve gas
causes ACh accumulation and overstimulation of cholinergic synapses throughout the CNS and PNS which leads to muscle paralysis and death by asphyxiation
what are the two ACh receptor subypes
nicotinic
muscarinic
what does the nicotinic ACh receptor subtype respond to, and what type of recepor is it
responds to nicotine agonist
ionotropic
what happens in nicotnic ACh receptor when ACh binds
cahnnel opens
Na+ and Ca2+ enter the cell and depolarize the membrane
mediates fast excitatory responses in CNS and PNS
how many subunits do nicotinic receptors have
5
what does coninuous activation of nicotinic receptors result in
receptors desensitize
channel remains closed even when the agonist is bound
recovers after a short time w no stimulation
what does prolonged activation of nicotinic receptors result in
depolarization block
persistent depolarization causes resting potential to be lost
cell cant be excited until agonist is removed and membrane repolarizes
what is a nicotinic receptor agonist and what does it do
succinylcholine
muscle relaxant used in some surgical procedures
causes depolarization block
what are two nicotonic receptor antagonists and what do they do
mecamylamine: blocks nicotinic receptors both in CNS and autonomic ganglia
d-tubocurarine: blocks muscle nicotinic receptors
what do muscarinic receptors respond to
muscarine
what types of receptors are muscarinic receptors
metabotropic
operate via second messenger and/or enhance K+ channel opening
where are muscarinic receptors found peripherally
caridac and smooth muscle in organs as well as insulin secreting cells of pancreas
where are M2 receptors and what do they do
cardiac
slows heart rate when activated
also acts as presynaptic autoreceptor in CNS
where are M3 receptors and what do they do
smooth muscle
activation results in conraction (digestive tract), and mediates other sevretory responses (ex salivation)
what is a muscarinic agonist
pilocarpine
parasympathomimetic agent
poisioning leads to exaggerated parasympathetic response (SLUDGE): salivation, lacrimation, urination, diarrhea, gastrointestinal distress, and emesis
what is a muscarinic antagonist
atopine and scopolamine
inhibit parasympathetic effexts
dialate pupils, redue seretions that clog airways, counteract holinergic poisoning
central effects are drowsiness, euphoria, amnesia, fatigue, dreamless sleep
high does make you: blind as a bat, mad as a hatter, red as a beet, hot as hades, dry as a bone, the bowel and bladded lose their tone, and the heart runs alone
what does ACh in the striatum do
regulation of movement depends on balance between ACh and DA
what does ACh in the pons do
project to midbrain DA neurons
regulates DA burst firing patterns
mediated by postsynaptic niotinic and muscarinic receptors
what does ACh in the basal forebrain cholinergic system (BFCS) do
intermixed with othe transmitters (GABA and glu)
plays a key role in regulating memory and cog functions mediated by forebrain regions, also facilitating attention
attention assay for ACh in mice
light flashes, they press L lever, light does not flash they press R lever
if they press the wrong lever its a miss or a false alarm
what happens to ACh in frontal cortex in rats performing the attention assay
increased ACh
