Week 1 - Neurotransmitters Flashcards
voltage gated channels in neurons
Na+, Ca2+
ligand gated channels in neurons
glutamate, GABA (Cl-), 5 HT, nicotinic (Na+)
types of channels in neurons
voltage gated, ligand gated
types of receptors in neurons
ligand gated channels, metabatropic, most are G coupled receptors
ligand gated channels in neurons as receptors
open briefly, fast action, ex: glutamate receptor
metabatropic receptors in neurons
receptor interacts with GTP-binding protein, modulates voltage gated channels (enhances K channels, inhibits Ca channels), typically for NTs, inhibitory, slower, G-coupled protein, activated G protein modulates ion channels
synaptic transmission
presynaptic membrane depolarizes, Ca2+ channels activated, Ca2+ entry into presynaptic axon terminal - promotes vesicle docking, release of vesicular contents, NT diffuses across synapse, NT binds to receptor and changes postsynaptic membrane potential by depolarizing (excitatory) or hyperpolarization (inhibitory) or presynaptic inhibition
mechanisms of action of drugs on NT
block presynaptic action potential, increase NT synthesis, change NT storage, change metabolism of NT, change NT release, change NT reuptake, change NT degradation, change NT receptor, change post synpatic ion conductance
hierarchical neuronal systems
alinged linearly, ex: sensory perception and motor control
diffuse neuronal systems
not highly ordered, effect many regions of the brain with diffusion of NT, ex: monoaminergic neurons - norepinephrine, dopamine, 5 hydroxytryptamine
neurons
release NT in response to depolarization, synthesize and store NT
glutamate
NT, hierarchical, excitatory, motor pathways, acts on AMPA, NMDA and Kainic acid receptors; can inhibit NT presynaptically
AMPA receptor
glutamate + AMPA acts on it, motor pathway, increased Na+ and K+, excitatory
NMDA receptor
glutamate + NMDA acts on it, memory, needs depolarized membrane to work, increases Ca2+, Na+, K+, glycine, excitatory
Kainic acid receptor (kainate)
glutamate + kainate works on it, excitatory, increases Na+ and K+, motor pathways
GABA (gamma-aminobutyric acid)
NT, hierarchical, inhibitory, motor, take away GABA and lose control of fine movements
GABA-a
Cl channel GABA receptor, Cl- channels activated = cell hyperpolarization
GABA-b
metabatropic GABA receptor, augements K+ or inhibits Ca2+ channels, inhibits adenylyl cyclase
Benzodiazepine
activate GABA receptors, cause sedation through neuronal inhibition
Baclofen
GABA receptor agonist, relaxes muscles
glycine
NT, hierarchical, inhibitory, motor, in brainstem and spinal cord, receptor is Cl- permeable = hyperpolarizing
strychnine
glycine receptor antagonist, blocks inhibition of motor activity = spastic paralysis
acetylcholine
NT, diffuse, excitatory, cognitive (memory), nicotinic and muscarinic receptors
nicotinic receptor
for acetylcholine, motor, ligand gated Na+ channel that causes depolarization, 5 transmembrane subunits, each subunit 4 transmembrane alpha helices, 2 ACh binding sites
muscarinic receptor
metabotropic receptor, reduces cAMP or increases Ca2+ or increases K+ permeability, cognitive function and memory
dopamine
NT, diffuse, inhibitory (motor stimulation via inhibiting inhibitor GABA), D1 and D2 receptors
D1 receptors
for dopamine, suppresses GABA release (inhibits an inhibitor of movement), increases K+ conductance, substantia nigra, depleted in Parkinson’s, likely associated with Tourrette’s
D2 receptors
for dopamine, limbic, slow inhibitory action, antipsychotics antagonize this receptor, some antidepressants prevent dopamine reuptake, involved in psychoses
norepinephrine
NT, diffuse, inhibitory, motor, increases K+ conductance, acts on alpha2 receptors
alpha 2 receptors
for norepinephrine, increases K+ conductance, receptor agonists are muscle spasmolytics
alpha 1 and beta receptors
for norepinephrine, attention and arousal
serotonin (5 hydroxytryptamine)
NT, diffuse, abundant in midline pons, excitatory, ionotropic and metabotropic receptors
5HT3 receptor
for serotonin, ionotropic, excitatory, conducts cations
5HT2a receptor
for serotonin, metabotropic, inhibitory, block receptor to help schizophrenia and bipolar, serotonin reuptake inhibitors increase serotonin at this receptor = anti-depressant
opiods
NT, diffuse, inhibitory, suppress pain, acts on mu / delta / kappa receptors, decreases Ca+ and cAMP, works in spinal cord
thujone
molecule in l’absinthe, GABAa receptor blocker, has a depressive effect
biogenic amines
group of NT that are small and amino acid related, enzymes that make NT made in nucleus and transported down axon slowly, look like many small vesicles in axon terminal
neuropeptides
group of NT that are large peptides, made in nucleus and transported down axon quickly on microtubule tracks, enzymes modify at axon terminal
definition of NT
present at synapse, released when neuron is stimulated, receptors for NT, NT gets same response and has agonists / antagonists
recycling of synpatic vesicles on presynaptic terminal
takes 1 min, exocytosis - edosome budding, docking, priming, fusion; endocytosis - budding, back to endosome
botulinum and tetanus toxins
effect SNARE proteins involved in vesicle fusion, Clostridium spcs. toxins, Zn+ proteases that cleave SNARE proteins
latrotoxin
triggers vesicle fusion and release of contents without Ca2+, black widow spider venom
VGLUT
presynaptic protein, vesicular glutamate transporter
V-ATPase
presynaptic protein, vesicular ATPase transporter
SNAP25 / syntaxin / synaptobrevin
presynaptic protein, involved in docking and fusion of vesicles
SNARE proteins
alpha helices, docking and fusion of vesicle, v-SNARE and t-SNARE
ionotropic receptors in neurons
for NTs, fast, ligand-gated ion channel
acetylcholine synthesis
enzyme choline acetyltransferase (ChAT), acetyl CoA + choline –> acetylcholine (ACh)
acetylcholine degradation
enzyme acetylcholinesterase (AChE), acetylcholine (ACh) –> acetic acid + choline
curare
antagonist at nicotinic ACh receptor
atropine
antagonist at muscarinic ACh receptor
ACh cycling at presynaptic neuron and synapse
ACh vesicle –> synapse –> nicotinic or muscarinic receptor –> AChE breakdown into acetic acid and choline –> choline / Na+ cotransporter –> ChAT makes ACh from choline and acetyl CoA –> ACh transporter into vesicle
nerve agent
organophosphate, chemical weapon, serine gas, inhibits AChE
atropene
Tx nerve agent, blocks stimulation at muscarinic receptor
tupan
tx nerve gas, reactivates AChE, problem - can’t get into brain
glutamate cycling between neurons and glia (astrocytes)
(presynaptic terminal) glutamine + enzyme glutaminase –> glutamate –> enters vesicle via VGLUT –> enters synpase –> interacts with glutamate receptors –> taken up by astrocyte via EATT –> enzyme glutamine synthase –> glutamine –> release by astrocyte via EATT –> taken up by neuron via EATT (excitatory amino acid transporter)
excitotoxicity
unrestrained release of glutamate at synapse, leads to cell death of postsynaptic cells, stroke / trauma / seizure can allow too much Ca2+ and Na+ into postsynaptic cell, Ca2+ –> makes NO radical and CaMKs for mitochondrial damage and activates proteases for nuclear damage, Na+ –> Cl- influx and water swelling / cell lysis
action of endocannabinoids
Ca2+ enters postsynaptic cell –> enzyme releases endocannabinoids from postsnyaptic cell –> taken up by presynaptic cell via cannabinoid receptor (CB1) –> G protein activated –> opens CA2+ channels on presynaptic cell –> vesicular release
