Test 1: Review/Membrane and Synaptic Physiology Flashcards
(115 cards)
1
Q
Where does info transfer in neuron?
A
synapse
2
Q
What leads to complex neural control system?
A
convergence and divergence
3
Q
what does Intracellular recording electrode measure?
A
measure membrane electrical potential
4
Q
What is the ground?
A
extracellular space
5
Q
What is the electric potential?
A
Between electrode and ground
6
Q
What is resting potential?
A
Potential at equilibrium
If equal on both sides, then zero. But if stuff has to cross, it will change
7
Q
What is the transmembrane potential?
A
A function of cell’s ability to maintain concentration gradients of different ion species across cell’s membrane.
8
Q
A rest membrane potential primarily determined by
A
K+ ions, tend to flow OUT along concentration gradient
9
Q
As K+ flow out
A
other cations in. Electrical gradient
10
Q
Equilibrium potential is a
A
linear function of the log of the concentration ratio
11
Q
Nerst Equation: getting equilibrium with 1 ion only
E(ion) = Transmembrane voltage at equilbirum
A
RT/zF ln (ion out)/(ion in)
Cations on top.
12
Q
2 chamber: where do ions flow?
A
For K+
if greater than -58, go left
if lower than -58, go right
13
Q
Why is the resting membrane potential not the equilibrium potential for K+?
A
Because determined by multiple ions
14
Q
E (Na+)
E (K+)
E (Cl-)
E (Ca2+)
A
E(Na+)= +56mV
E (K+)= -102mV
E (Cl-)= -76mV
E (Ca2+)= +125mV
15
Q
Goldman Equation
A
Em = RT/F ln (p(ion) + p(ion)/p(ion) + p(ion)
Cations have “out” on top
PK: PNA: PCL is 1: 0.04: 0.045
Membrane potential function of relative permeabilities
16
Q
Na/K+ pump
A
main gradients ATPase convert ATP to ADP and phosphate restores ion concentration gradients maintains resting potential electrogenic - 3Na+ out, 2K+ in 20-40% energy consumption
17
Q
Hyperkalemia
A
high K+ depolarized excitable membrane
cardiac muscle become hyperexcitable, fibrillation- uncontrolled contraction.
Hypoxia/stroke: ATP runs down, cell can’t maintain differential gradient, depolarized, increased excitotoxicity.
18
Q
The time required to reach __% o final voltage is membrane time constant tau
A
63%
resistance * capacitance
19
Q
why are membranes SLOW to depolarize?
A
capacitance properties
20
Q
Time constant is time when voltage response rise to
A
1-(1/e) or 63% of Vinfinity (steady state membrane charge)
21
Q
You need a (longer/short) tau to fire AP.
A
Longer
22
Q
What is ^?
A
Length constant
Depends on membrane resistance
23
Q
Calculate ^
A
SQRT(membrane resistance) /
SQRT(intra r + extra r)
best passive current: lower intra/extra r and higher membrane resistance
24
Q
Increase strength of depolarization: does this make bigger AP?
A
no, more AP but not bigger
25
Passive responses
below thershold
26
active response/conductance
above threshold
27
negative current
hyperpolarization
28
Rising phase
rapid depolarization
29
overshoot
positive to 0 mV
30
Falling phase
repolarization
31
undershoot
hyperpolarization following the spike
32
Voltage Clamp Technique
studies AP
clamp amplifier injects current to axon through 2nd electrode
By measuring the current injected, determine amp. and time of ionic current across membrane `
33
What happens in squid axon if you replace Na+ with choline?
only outward current now
34
Does K+ activate faster or slower than Na+?
Slower
35
Block Na+
TTX
36
Block K+
TEA
37
Steps of AP
1. activate Na+ = Na+ ions into cell, depolarize, activates K+ channels
2. Inactive Na+
3. Hyperpolarize K+
4. Na+ inactive portion removed
38
Patch clamp allows for
individual or small numbers of ion channels
39
Cell-attached recording
response of channels/channels pipette has covered
40
Whole-cell recording
more suction, membrane disrupted
| electrode interior continuous with cell interior
41
Inside-out recording
intact membrane, suction away from cell
42
Outside-out recording
pull back some membrane, and have it reform such that cytoplasmic side frees electrode.
43
Na+ conductance
```
rapid onset (activation)
rapid offset (inactivation)
```
44
K+ conductance
slow onset/offset
after hyperpolarization (undershoot)
45
Refractory period: absolute refractory period
Na+ channel inactivation
46
relative refractory period
afterhyperpolarization
higher threshold
47
If AP travels in both directions, what stops it from going back and forth?
refractory period
AP travels at specific rate.
48
_______ measures the rate at which electrical impulses move along a nerve.
Used to diagnose disorders of the _______
nerve conduction study (NCS)
peripheral nerves and muscle
49
Action Potential Propagation: Conduction of AP
combine passive, active currents
passive spread of cations depolarizes next segment of membrane. Next segment crosses threshold. AP generation occurs, causing passive current spread to next segment: Regeneration of AP.
50
____ inactivation produces refractory period and prevents backpropagation
Na+
51
______ repolarize membrane.
voltage-gated K+ currents
52
Faster axons are
big and myelinated
53
Why are larger axons faster?
less internal resistance
54
Why myelin faster?
less capacitance
insulates axon
restriction to nodes of ranvier
55
capacitive and ionic currents are highest at ____
nodes of Ranvier
56
higher capacitance at unmyelinated nodes ...
slows AP
57
Loss of myelin means local circuits must charge...
larger areas, and reduce r means less change in V membrane.
58
Structure of voltage gated channels
```
integral proteins
may have several spanning domains
pore
voltage sensor - internal domain
selective permeability
```
59
What makes and maintains ion gradients?
ATPase PUMPS
60
Channelopathies - small but critical alteration in ion channel gradients
Familial Hemiplegic Migraine (FHM)
migraine attacks the last 102 days, sever headaches vomiting
****Ca2+ Channel
61
Channelopathies small but critical alteration in ion channel gradients
Episodic ataxia type 2 (EA2)
recurrent attacks of abnormal limb movements and severe ataxis (incoordination), headache, nauseas (stomach distress)
usually attacks are triggered by emotional stress, exercise, or alcohol and last for a few hours
****Ca2+ Channel
62
Channelopathies small but critical alteration in ion channel gradients
X-linked congenital stationary night blindness (CSNB)
recessive retinal
night blindness, decrease acuity, myopia, nystagmus, strabismus, rod photoreceptors not functional
paralysis: decreased electrical excitability in muscles
**Ca2+ Channel
63
Channelopathies small but critical alteration in ion channel gradients
Episodic ataxis type 1 (EA1)
brief episodes of ataxis (incoordination)
increased electrical excitability due to impaired AP repolarization
****K+ Channel
64
Channelopathies small but critical alteration in ion channel gradients
Benign familial neonatal convulsion (BFNC)
frequent brief seizures during first week of life and disappearing spontaneously within a few months
Decreased K+ efflux through v-gated K+ channels and increased electrical excitability
****K+ channel
65
Generalized epilepsy with febrile seizures
increase Na+ influx and INCREASED electrical excitability in the brain
66
Myotonia
increase Na+ influx and INCREASED electrical excitability and muscle stiffness (muscles)
DECREASE in Cl- conductance (muscles)
67
Paralysis
decreased Na+ influx that causes DECREASE in electrical excitability (muscles)
68
Paper: SCN9A channelopathy causes congenital inability to experience pain
nociceptive neurons.
mutations alpha subunit of Na 1.7
No pain
Each family had slightly different mutation
nonsense and frame shift mutations in the families.
na+ channels expressed HEK cells
Why? NOT SENSITIVE TO MEMBRANE VOLTAGE, SO THEY DON"T FIRE AP
69
Electrical synapse characteristics
faster than chemical
connected cells make electrical syncytium.
Gap junctions. Synchronize neurons.
6 connexins = 1 connexon
open and close randomly, increased probability of opening under specific conditions, elevated Ca2+, depolarization
using reflex pathways
70
Chemical synapse characterisitics
no direct contact, neurotranmitters in cleft
71
Methionine Sulfoximine
inhibits glutamate synthesis (limit stroke damage)
72
Carbidopa
inhibits dopamine synthesis (used in Parkinson's)
73
2. How would you stop AP arriving at terminal?
Novacaine, Na+ channel blocker
74
3-5. How do you stop depolarization and influx of Ca+ and vesicle stuff?
alpha latrotoxin- causes ca2+ independent transmitter release, convulsant
75
6. How do you block transmitter release?
Tetanus toxin, blocks GABA release, convulsant
76
7. Receptor binding interference
1) Mirapex- binds and activates dopamine receptors, Parkinson's treatment
2) Diazepam (valium)- GABA agonist treatment for epiespy, anxiety
3) Clozapine- serotonin receptor agonist, antipsychotic
77
10. Example that stops reuptake
SSRIs, antidepressants
78
11. Degradation
cholinesterase, inhibitors, neostigmine
79
Experimental setup: voltage clamp of presynaspe membrane: what did we learn about calcium and shit?
cadmium block and no EPSP.
| SO calcium is needed for transmitter release
80
SNARE:
Presyn
Postsyn
pre: SNAP25 and syntaxin
post: synaptobrevin
81
Synaptotagmin
Ca2+ sensor
triggers membrane transmitter release
82
Clostridium bactira
c. TETANUS
Botulism
PROTEASE. cleaves SNARE
block synaptic transmission
83
Alpha-latrotoxin
binds to synaptotagmin causes calcium independent transmitter release
84
Botulism
food bourne.
blurry vision, dry mouth, paralysis
fix with antitoxins
floppy baby
botox
85
Tetanus
bacteria through puncture
blocks release of inhibitory NT, loss of inhibition on spinal motor neurons.
Descending pattern of symptoms
86
Synthesis of DEN (Catecholamines)
Phenylalanine
PHENYLALINE HYDROXYLASE
L-tyrosine
TH- RATE LIMITING
3,4, dihydroxyphenylanine (DOPA)
L-AADC
Dopamine
DOPAMINE-BETA-h AND VMAT TO VESICLE
norepinephrine
PMNT
Epinephrine
87
Reserpine
treats high blood pressure/psychosis
block catecholamine transmission
stops it getting in vesicles
88
VMAT1
adrenal glands
89
VMAT2
catecholamine and 5HT neurons
90
3 ways of inactivation
1. diffusion
2. reuptake
3. enzymatic inactivation
91
MAO -A
affinity for NE and 5HT
inhibited by clorgyline
slow acting
92
MAO -B
dopamine / o-phenylethlamine
inhibited by deprenyl (MPPP)
antidepressant, neuroprotective effects
Parkinson's
sexual dysfunction
93
COMT
inhibitors used to prevent inactivation of DOPA
94
Tricyclic antidepressants target
NE
95
Serotonin synthesis
Tyrptophan
Enzyme: Tryptophan hydroxylase (rate limiting)
5-hydroxytryptophan (5-HTP)
Enzyme: AADC
5-HT
96
Serotonin facts
accumulated in vesicles by _____
inactivated by reuptake through ____
degraded by ____
Treaptuic effect slower, probably tied to downregulation of __________ on presynaptic membrane.
accumulated in vesicles by VMAT2
inactivated by reuptake through EXOCYTOSIS
degraded by MAO
Therapeutic effect slower, probably tied to downregulation of 5-HTA1 autoreceptors on presynaptic membrane.
97
JAMA on antidepressants
good if severe depression
98
Histamine synthesis and facts
Histidine
Histidine decarboxylase
Histamine
Transport by VMAT
degraded by histamine methyltransferase and MAO
mediate attention/arousal.
Receptors G-coupled.
antihistamines cause sedation.
antagonists used for motion sickness
99
gamma-aminobutyric acid (GABA)
GAD requires pyridoxal phosphate cofactor, derived from vitamin b6
alpha-ketogluatarate
GABA-T (mitochondria)
glutamate
GAD (cytosol)
GABA
Vesicle transport: VIAAT
reuptake: GAT
* ***degraded by : GABA-T (makes GHB)
100
GABA receptor subtypes
A/C: ionotropic, increase Cl- conductance
B: metabotropic, increase K+ conductance
Benzo: antianxiety
Barb: hypnotics, anesthesia, epilepsy `
101
Glutamate
excitatory amino acid
responsible for most fast excitatory neurotransmission in mammalian brain
derived from alpha-ketoglutarate
transported by VGluT
inactivated by reuptake EAA transporters located on neurons and glia
102
Acetylcholine
CAT makes it (Chat transfers acetyl to choline)
ACE degrades it
vesicles by VAChT
103
Cholinesterase inhibitors
sarin, malathion, neostigmine
Block ACE, prolong Ach
104
Ionotrophic
large, multisubunit
complex
fast onset/reversal
[N]
AMPA, Kainate, NMDA
105
Metabotrophic receptors
single polypeptide
7 transmembrane domain
activated leads to binding and activating of G proteins
Slow onset/duration
[M]
beta-adrenergic
106
[N]
2x alpha subunits
4 different subgroups
snake venom
5 subunits - 2 alpha, 1 beta, 1 gamma, 1 delta
ring and central poor
N-terminus in Extraceullar space
Each subunit has 4 transmembrane spanning segments
TM2 regions line the pore
Rings of - charge act as selective filter
Leucine residues in TM2 block ion channel
107
How are nACh [N] blocked?
Leucine residues in TM2 segments form ring, block central pore
Ach binds to receptors in pore, TM2 rotates
ion flow through expanded central pore and through hole in lateral walls of intracellular portion of receptor
108
Metabolic G protein coupled receptors
single polypeptide
transmitter binding leads to g protein activation
activated G protein couples to downstream effectors
slow onset longer duration
7 transmembrane domains
extraceullar N terminus
intracellular c terminus
long 3rd intracellular loop interacts with G protein, specificity
GTP bond = activation
109
How are G proteins activated?
1) Collision coupling - transient association between the activated receptor and the G protein. Subsequent collision coupling can occur between one activated receptor and several G proteins leading to amplification of signal
2) interaction of i3 of GPCR with g protein causes conformation change allowing exchange GDP for GTP
3) activated GTP-bound G proteins interact with effector proteins
4) activity of G protein is limited by GTPase activity that breaks down GTP for GDP
Ligand bind on TMS and TM6 --> Cleavage in i3
110
G protein active state
beta and gamm
alpha-GTP
What turns off alpha subunit: GAP
E3 binds to alpha subunit
111
G protein: when NT binds to receptor, ______ activates receptor
conformation change in i3 loop
112
Over 1/2 of all prescription drugs work through
G ptrotein coupled receptors
113
G protein couple receptors effects
ion channels cAMP/cGMP
intracellular enzymes
gene transcription
114
Second messengers
downstream of effector molecule
cAMP, phosphoinositol metabolites, calcium
target kinases that change activity of enzymes, metabolism, and ion flow
2nd messengers and receptors are held in close proximity by proteins that bind to specialized domains
115
Excitation of skeletal muscle
brain: upper MN
spine: lower MN --> release Ach to get PSPs
Motor unit = motor neuron and group of skeletal muscle fibers in innervates
finer control = smaller motor unit
induces Ca2+ influx. (CHEMICAL SYNAPSE)
troughs with receptors inside
increase Na+ permeability, depolarization causes +
end plate potential in the post synaptic muscle
