Neural Communication Flashcards
How does the presence or absence of channels with differing properties affect neurons?
1) how they fire to brief or continuous stimulation
2) how excitable or non-excitable in general
How can the properties of channels within a neuron be changed and what is the consequence?
post-translational modifications (like phosphorylation) which change how the neurons respond to stimuli or how well they signal to other neurons
How does the diversity of electrical properties arise?
1) from a diversity of ion channel types
2) post-translational modifications
What are some ion-specific and ligand-gated channels formed from?
different combinations of channel forming subunits
What associates with channel forming subunits?
diversity of modifying subunits
What is the basis of many types of neuromodulation?
post-translational modifications (primarily phophorylation)
What are K channels composed of?
4 separate subunits clustered together (diversity of subunits and sub-types of subunits)
What is a selectivity filter?
makes each channel specific to one type of ion
What is “water of hydration”?
water that is combined with other molecules to form a hydrate mineral
What must a potassium do to pass through a potassium channel?
remove all of its surrounding water molecules except two (one on front and one on back)
What must a sodium do to pass through a sodium channel?
sodium ion can pass through with up to three water molecules
What is the “delayed rectifier” family of K channels?
V2.1
What is the transient family of K channels?
V4.1 (also called “A” or IA channels)
What do the ligand-gated K channels respond to?
1) Ca
2) combined Ca and V-dep
3) chemical changes (pH)
What are the calcium activated K channels?
1) BK channel (Big g)
2) SK channel (Small g)
3) IK channel (intermediate g)
What is the notation of the BK channels and what is there defining characteristic?
- KCa1.x
- also voltage sensitive over a physiologically relevant range
What is the notation of the SK channels and what is there defining characteristic?
- KCa2.x
- blocked by apamin (component of bee venom)
What is the notation of IK channels and what do some consider them to be?
- KCa3.1
- some consider these a sub-type of SK
- not blocked by apamin
Which ligand-gated ion channels have an external ligand?
1) neurotransmitter receptor
2) acid sensing ion channel
Which ligand-gated ion channels have an internal ligand?
1) Calcium activated K+ channels
2) Cyclic nucleotide gated channels
What are statocyst hair cells an example of?
how channel properties can create complex electrical properties
Is the affinity for Ca high or low for CaK channels in statocyst hair cells?
low affinity for Ca
Are Ca channels and K channels tightly or loosely co-localized in statocyst hair cells?
tightly co-localized
Why is there a low affinity for Ca?
allows Ca to diffuse and potassium channels to close
Why is there tight co-localization between Ca and K channels?
creates a calcium domain so that CaK channels may open (since diffusion takes time)
What are the voltage-gated calcium channel families?
1) Cav 1.x: “L-type”
2) Cav 2.1: “P-type”
3) Cav 2.2: “N-type”
4) Cav 2.3: “R-type”
5) Cav 3.x: “T-type”
What are the characteristics of Cav1.x (L-type)?
1) blocked by dihrdropyridines
2) medium speed, moderate inactivation
What are the characteristics of Cav 2.1 (P-type)?
1) blocked by agatoxin from funnel web spider
2) fast open, little to no inactivation
What are the characteristics of Cav 2.2 (N-type)?
1) blocked by conotoxin GVII from cone snail
2) fast open, little to no inactivation
What are the characteristics of Cav 2.3 (R-type)?
1) resistant to blockers of P and N
2) fast, little to no inactivation
What are the characteristics of Cav 3.x (T-type)?
1) blocked by Ni2+ ions, synthetic blockers
2) slowest opening, very inactivating
3) low voltage activated
Which voltage gated calcium channel family is commonly used for fast neurotransmission?
Cav 2.1, Cav 2.2, Cav 2.3
What can many beta subunits do?
act to modify gating properties (e.g. inactivation)
What can change the opening probability?
phosphorylation
What is the “simplest bursting neuron”?
a central pattern generator with all inhibitory neurons that are driven by excitatory outside neurons
What 3 currents does a simplest bursting neuron need?
1) persistent Na current
2) voltage gated Ca
3) Ca dependent K
What would happen if you add Ca buffer to a simplest bursting neuron?
the cell would keep firing
What are some Na channel toxins?
1) tetrodotoxin (puffer fish)
2) saxitoxin (marine dinoflagellates)
What are some K channel toxins?
1) dendrotoxin (snake)
2) charybdotoxin (scorpion)
3) batrachotoxin (frog)
What does alpha-toxin from Leiurus scorpion do?
delays Na+ channel inactivation
What can toxins from venoms do?
block channels, lock them open, a or alter their activation or inactivation kinetics
What does the toxin apamin from bees do?
1) blocks SK Ca activated K channels
2) affects the afterhyperpolarization (reduces it) which in turn can affect firing rate/excitability of neuron to sustained input
What are “chnnelopathies”?
diseases caused by mutation in voltage gated channels (Na K, Ca channels)
What occurs during “generalized epilepsy with febrile seizures”?
slowing of Na+ channel inactivation leads to neuronal hyperexcitability
What happens during “benign familial neonatal convulsions”?
1) frequent seizures within the first week of life disappearing spontaneously within a few months
2) affects K+ channels
What is myotonia and what channel does it affect?
1) muscle weakness
2) Cl- channel
What are the main two categories of neurotransmitters?
1) small molecule
2) peptide
What are the classes of neurotransmitter molecules under “small molecule”?
1) Acetylcholine
2) Amino acids
3) Purines
4) Biogenic amines
What are the neurotransmitters classified as amino acids?
1) glutamate
2) aspartate
3) GABA
4) Glycine
What is the neurotransmitter classified under purines?
ATP
What are the subclasses of neurotransmitters under biogenic amines?
1) Catecholamines
a) dopamine
b) norepinephrine
c) epinephrine
2) Indoleamine
a) serotonin (5-HT)
3) Imidazoleamine
a) histamine
Which small molecule transmitters are not contained in vesicles and why?
1) endocannabinoids (lipid soluble)
2) nitric oxide (gas)
3) carbon monoside (gas)
4) adenosine (made from ATP in extracellular space)
What are peptide neurotransmitters composed of?
more than 100 peptides, usually 3-30 amino acids long
Where are peptide neurotransmitters produced?
made in cell body because they need ER and golgi for production
What are the steps in acetylocholine production?
1) glucose -> pyruvate
2) pyruvate -> acetyl CoA (in mitochondria)
3) Acetyl CoA + Choline -> acetylocholine (using chline acetyl-transferase)
How is choline brought into the cell?
Na+/choline transporter
How is acetylcholine degraded after use?
1) turned into acetate and choline by acetylcholinesterase
2) choline taken up by transporter for reuse
Where does acetylcholine production take place?
In the presynaptic terminal
What is the transport system to load vesicles?
1) proton-pumping ATPase
2) exchange of nt and H+
What are examples of toxins that bind postsynaptic receptors?
1) bungarotoxin
2) epibatidine
3) conotoxins
4) betel nut
What is bungarotoxin from and what does it do?
1) cobra alpha neurotoxin
2) nACh antagonists
What is epibaidine from and what does it do?
1) ecuadoran frog
2) nicotinic and muscarinic AChR
What is conotoxin from and what does it do?
1) several peptides from cone snail
2) some block presynaptic Ca channels but many also block postsynaptic Gky- and ACh receptors
What is the betel nut toxin and what does it do?
1) arecoline
2) muscarinic AChR agonist
What is the general architecture of ligand-gated receptors?
1) 5 subunits
2) need alpha
3) pore
What specifications in structure do acetylcholine (nACh) receptors need?
need 2 alpha subunits, need two nt to bind to open
What is the effect of needing two binding alpha subunits?
more sensitive to higher concentration because of increase in probability not affinity
What does myasthenia gravis do?
1) attacks nicotinic receptors
a) reduces # of receptors
b) disorganizes receptors
2) leads to muscle weakness
What is the treatment for myasthenia gravis?
neostigmine
What is the structure of metabotropic receptors?
1) g-protein coupled
2) no pore
3) neurotransmitter binding site and g-protein binding site
What receptor classes are metabotropic receptors?
1) glutamate
2) GABA
3) Dopamine
4) NE, Epi
5) Histamine
6) serotonin
7) purines
8) muscarinic
What receptor classes are ligand-gated receptors?
1) AMPA
2) NMDA
3) Kainate
4) GABA
5) Glycine
6) nACh
7) Serotonin
8) Purines
What are the steps in glutamate synthesis?
1) glutamine -> glutamate (using glutaminase)
How is glutamate taken up after being released?
1) Taken directly back into presynaptic terminal
2) taken up by glial cell
a) enters cell by excitatory amino acid transporter (EAAT)
b) glutamate -> glutamine (by glutamine synthetase)
c) released by SN1 channel
d) taken into presynaptic terminal by SAT2 channel
What is the voltage dependent “blocker” in NMDA receptors and how is it removed?
Mg2+
needs to bind two glutamates and be depolarized
What are NMDA receptors dependent on?
voltage and ligand dependent
What are the cofactors for NMDA receptors?
glycine or serine
Compare NMDA and AMPA.
1) AMPA is quick to turn on and off, whereas NMDA is longer lasting
2) NMDA has Ca permeability (all but one AMPA do not pass Ca)
What are the three classes of iono GluR?
1) NMDA
2) AMPA
3) kainate receptors
What is the Ca-permeant AMPA sub-type also involved in?
synaptic plasticity
What is the structure of AMPA receptors?
dimer of dimers: glurR2-glu-R2 + dimer of gluR1, 3 or 4
What does the AMPA receptor lack if it is Ca permeable?
lack gluR2
What is the general process of GABA synthesis?
1) glucose -> glutamate
2) glutamate -> GABA (by glutamic acid decarboxylase and pyridoxal phosphate)
What is GAD?
glutamic acid decarboxylase (a marker of GABA synthesizing terminals)
How is GABA taken up after release?
1) directly into presynaptic terminal (GAT) and into vesicle (VIATT)
1) directly into presynaptic terminal (GAT) and to mitochondria for breakdown
3) into glial cell (GAT)
What is GAT?
a GABA and Na co-transporter
What is the process of glycine synthesis?
1) glucose -> serine
2) serine -> glycine (by serine hydroxymethyltransferase)
How is glycine taken up after being released?
1) directly into presynaptic terminal by glycine-Na transporter
2) into glial cell by glycine-Na transporter
What do many of the sites where ligands can bind cause?
modulation of receptor function (potentiate or block)
What binding sites modulate efficacy of GABA binding?
1) barbiturates
2) steroids
3) picrotoxin
What ions flow through GABA receptors?
chloride ions
What happens when GABA is increased?
shut off neurons (inhibitory except in early development because of different chloride transporters)
Which site is very addictive?
barbiturate site
What are some clues in the “Mother’s Little Helper” song?
1) little yellow pill
2) tranquilize
3) help through the night
4) overdose
What pill might they be talking about in “Mother’s Little Helper”?
1) Valium
2) Meprobamate
3) Carodosoprodol
Why is GABA excitatory in immature neurons and inhibitory in mature neurons?
1) high concentration of Cl inside the cell (immature) so Cl leaves and causes depolarization
2) low concentration of Cl inside causes Cl to enter and hyperpolarize (mature)
What are the steps in the biosynthetic pathway for catecholamine nts?
1) Tyrosine -> Dihydroxyphenylalanine (DOPA) (by O2 + tyrosine hydroxylase)
2) DOPA -> dopamine (by -CO2, DOPA decarboxylase)
3) dopamine -> norepineprine (by O2 + dopamine-beta hydroxylase)
4) norepinephrine -> epinephrine (by RCH3+ phenylethanol-amine N-methyl-transferase)
What is the rate limiting step in the biosynthetic pathway for catecholamine nts?
tyrosine hydroxylase (if increased the amount of synthesis increases)
What is the drug L-DOPA used for?
help increase the amount of dopamine synthesized by neurons as a therapy for Parkinson’s
Where are catecholamines released from?
relatively small groups of neurons in hindbrain/brainstem and project
What is the process of the synthesis of histamine?
histidine -> histamine (by -CO2, histidine decarboxlyase)
What is the process of the synthesis of serotonin?
1) Tryptophan -> 5-Hydroxytryptophan (by O2 + tryptophan-5-hydroxylase)
2) 5-hydroxytryptophan -> serotonin (5-hydroxytryptamine) (by -CO2, aromatic L-amino acod decarboxylase)
What are the effects of tetrahydrocannabinol (THC)?
motor learning, synaptic plasticity, memory/learning, appetite, pain sensation, mood
