Exam 1 (chpt 7 acetylcholine) | Quizlet

acetylcholine synthesis is catalyze by

the enzyme choline acetyltransferase

what are the adjective forms of acetylcholine

Ach; colinergic

acetylcholine is synthesized in one step from _____ and _______, catalyzed by ____

choline

acetyl coenzyme A (acetyl CoA)

cholin acetyltransferase (ChAT)

ChAT is found only in neurons that use

ACh as a transmitter

rate of synthesis depends on availability of

precursors and rate of cell firing; there are no inhibitors of ChAT

synthesis of acetylcholine is by

choline acetyltransferase

what are the precursors to making acetylcholine

choline

acetyl coa

acetylcholine + coenzyme A

many different drugs and toxins can alter

acetylcholine storage and release

ACh is loaded into synaptic vesicles by

vesicular ACh transporters (VAChT)

VAChT can be blocked by _____ = reduces amount of ACh released when neurons fire

vesamicol

where does the process of ACh synthesis and metabolism, presynaptic choline uptake, and vesicular ACh uptake and release occur?

at the synapse

ACh release is affected by

toxins

black widow spider venom causes

massive release of ACh in the PNS

botulism toxin blocks ACh release by

preventing fusion of synaptic vesicles with nerve terminal membrane; causes muscular paralysis

deadly poison, therapeutic remedy, and cosmetic aid

botulinum toxin

botulinum toxins A through G are produced by the

anaerobic bacterium Clostridium botulinum

the botulinum toxin proteins are taken up selectively by _____ _____, including at the Neuromuscular junction, and fibers innervating smooth muscle and secretory glands

peripheral cholinergic nerve terminals

botulinum toxins are used in treating disorders characterized by

involuntary muscle contractions, as a pain reliever, and cosmetically (Botox)

what is responsible for acetylcholine breakdown

acetylcholinesterase

breaks ACh down to choline and acetic acid; four subunits combine to form a tetramer (G4)

acetylcholinesterase (AChE)

three forms of AChE

- soluble: free G4 in the cell

- G4 tethered to the cell membrane - in a position to allow rapid breakdown

A12 - at neuromuscular junctions; 12 subunits; very rapid breakdown of Ach allows muscle to relax before next contraction

three main forms of ACHe occur within the

brain and peripheral nervous system

choline is taken back up by

choline transporters

choline transporters can be blocked by _____

hemicholinium-3 (HC-3) - ACh production declines

Drugs that block AChE prevent breakdown

of ACh

ACh effects _____ = useful for disorders in which

increase

cholinergic transmission is deficient, but can be toxic or fatal

donepezil (Aricept)

rivastigmine (Exelon)

galantamine (Reminyl)

they are AChE reversible inhibitors used in treatment of age-related dementia

reversible AChE inhibitor that crosses blood-brain barrier and affects the CNS; used for glaucoma (applied directly to eyes) but toxic if given systemically.

physostigmine (eserine)

: irreversible AChE inhibitors; used as insecticides; "nerve gasses" are more toxic versions, such as sarin and soman.

organophosphorous compounds

•Troops in Iraq were given the reversible AChE inhibitor _____ as a nerve gas antidote: temporary interaction of ______with the enzyme protects AChE from permanent inactivation

pyridostigmine

several neuromuscular disorders are associated with

abnormal cholinergic functioning at the neuromuscular junction

•autoimmune disorder in which antibodies against muscle cholinergic receptors are produced; leads to severe muscle weakness and fatigue

myasthenia gravis

synthetic analogs of physostigmine that don't cross the blood-brain barrier

treated with neostigmine (prostigmin) and pyridostigmine (mestinon)

in myasthenia gravis, antibodies interfere with

cholinergic transmission at the neuromuscular junction by binding to and blocking the muscle ACh receptors

result from mutations in genes that encode ChAT or AChE

myasthenia syndromes

when there is low ChAT

insufficient amounts of ACh are released at the neuromuscular junction

Deficient AChE: persistently elevated levels of ACh at neuromuscular junctions lead to

desensitization of receptors and reduced cholinergic transmission

which chemical could be used to identify the location of cholinergic neurons?

c. choline acetyltransferase

cholinergic neurons play a key role in the functioning of both the

peripheral and central nervous systems

what preganglionic and ganglionic neurons are cholinergic?

preganglionic neurons of both branches of the autonomic nervous system are cholinergic, as are the ganglion neurons of the parasympathetic system

what is the transmitter of the sympathetic ganglionic neurons

norepinephrine

pre and post neurons in the parasympathetic branch

pre - acetylcholine

post - acetylcholine

pre and post neurons in the sympathetic branch

pre - acetylcholine

post - norepinephrine

in the brain, cell bodies of cholinergic neurons are

clustered in only a few areas

interneurons in the _____: what function do they have?

striatum

regulation of movement depends in part on the balance between ACh and dopamine (DA)

in Parkinson's disease what are the drug levels?

low DA levels cause transmitter imbalance; anticholinergic drugs may be used for treatment

orphenadrine (Norflex), benztropine mesylate (Cogentin), trihexyphenidyl (Artane), procyclidine (Kemadrin), and biperiden (Akineton)

anticholinergic drugs used in Parkinson's

•neurons in several brain areas; origin of cholinergic innervation of the cerebral cortex, hippocampus, and other limbic system structures.

basal forebrain cholinergic system (BFCS)

different components of the BFCS have

different roles in cognition

cholinergic projections from the medial septum and diagonal band to the hippocampus are involved in

encoding of declarative memories

projections from the nucleus basalis/substantia innominate to the prefrontal cortex are important for

maintaining sustained attention

optogenetic experiments in mice show that bursts of ACh release from BFCS neurons play a key role in

detecting and responding to learned sensory cues

Cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei (LDTg and PPTg) project to the

basal ganglia and thalamus; others to the lower brainstem and spinal cord

cholinergic neurons have multiple roles, including

stimulation of midbrain dopamine neurons and initiation of REM sleep

dopamine neurons are important for

drug reward and reinforcement

there are two acetylcholine receptor subtypes

nicotinic and muscarinic

respond to the agonist nicotine, an alkaloid in the tobacco plant

nicotinic receptors

respond to muscarine, an alkaloid first isolated from fly agaric mushrooms

muscarinic receptors

Nicotinic acetylcholine (nAChRs) receptors

ionotropic, mediate fast excitatory responses in both the CNS and the PNS

when ACh binds, the channel opens, and what happens

Na+ and Ca2+ enter the neuron or muscle cell, which depolarizes the cell membrane

each Ach receptor has how many subunits

5

- a, b, y, s, and e (there are many types of a and b subunits)

all receptors have a subunits

subunit composition determines key features of a receptor such as

affinity of binding sites

ionic selectivity

allosteric binding sites

channel opening

closing kinetics

ionotropic receptors can be

closed

open

desensitized

when ionotropic receptors are desensitized, what happens?

channel is closed and won't open even if an agonist binds

prolongued exposure to an agonist enhances the rate of conversion to the desensitized state, can spontaneously

resensitize

the ACh receptor can exist in three different states

open

closed

desensitized

even with continuous agonist exposure, not all receptors are

desensitized, and they produce a persistent depolarization of the cell membrane

resting potential of the membrane is lost, and the cell cannot be excited until agonist is removed and membrane repolarized.

depolarization block

powerful muscle relaxant; resistant to breakdown by AChE; thus it continuously stimulates the nAChRs and induces a depolarization block of the muscle cells.

succinylcholine (suxamethonium)

•antagonist at neuronal nAChRs in the CNS and autonomic ganglia; antihypertensive agent, no longer used.

mecamylamine (inversine)

antagonist of muscle nAChRs; paralyzing active ingredient of curare

d-tubocurarine

such as imidacloprid, acetamiprid, and thiacloprid: receptor agonists selective for insect nAChRs; absorbed and distributed throughout treated plants; probably harms beneficial insects as well as crop pests.

neonicotinoids

muscarinic receptors are

metabotropic - operate via second messengers

five subtypes of muscarinic receptors

M1, M3 and M5 activate the phosphoinositide second messenger system (excitatory)

M2 and M4 inhibit

stimulate ___

inhbit ___

cAMP synthesis,

k+ channel opening

nerve terminal Ca2+ channel opening (inhibitory)

muscarinic receptors in the neocortex and hippocampus play an important role in the

cognitive effects of ACh

muscarinic receptors in the striatum are involved in

motor function

M5 in the brain is expressed primarily in the

hippocampus, hypothalamus, and midbrain DA areas, may have a role in reinforcement

outside of the brain, muscarinic receptors are found in

cardiac and smooth muscle, activated by ACh released from parasympathetic postganglionic fibers

drugs used to treat many psychiatric disorders block

peripheral muscarinic receptors, especially in secretory glands

causes dry mouth effect

Naturally occurring muscarinic receptor agonists: muscarine, locarpine, arecoline (parasympathomimetic agents); mimic

effects of parasympathetic activation; high doses can be fatal

): atropine, scopolamine; found in henbane and deadly nightshade. Some have medical uses, such as atropine for dilating pupils

muscarinic receptor antagonists inhibit parasympathetic action (parasympatholytic agents)

from Amanita muscaria mushrooms

muscarine

from the leaves of the South American shrub Pilocarpus jaborandi

pilocarpine

found in the seeds of the betel nut palm Areca catechu.

arecoline

what is the active ingredient in curare?

muscle nAChRs antagonist