Test 1: Review/Membrane and Synaptic Physiology Flashcards

1
Q

Where does info transfer in neuron?

A

synapse

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2
Q

What leads to complex neural control system?

A

convergence and divergence

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3
Q

what does Intracellular recording electrode measure?

A

measure membrane electrical potential

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4
Q

What is the ground?

A

extracellular space

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5
Q

What is the electric potential?

A

Between electrode and ground

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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

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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.

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8
Q

A rest membrane potential primarily determined by

A

K+ ions, tend to flow OUT along concentration gradient

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9
Q

As K+ flow out

A

other cations in. Electrical gradient

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10
Q

Equilibrium potential is a

A

linear function of the log of the concentration ratio

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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.

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12
Q

2 chamber: where do ions flow?

A

For K+

if greater than -58, go left
if lower than -58, go right

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13
Q

Why is the resting membrane potential not the equilibrium potential for K+?

A

Because determined by multiple ions

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14
Q

E (Na+)
E (K+)
E (Cl-)
E (Ca2+)

A

E(Na+)= +56mV
E (K+)= -102mV
E (Cl-)= -76mV
E (Ca2+)= +125mV

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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

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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
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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.

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18
Q

The time required to reach __% o final voltage is membrane time constant tau

A

63%

resistance * capacitance

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19
Q

why are membranes SLOW to depolarize?

A

capacitance properties

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20
Q

Time constant is time when voltage response rise to

A

1-(1/e) or 63% of Vinfinity (steady state membrane charge)

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21
Q

You need a (longer/short) tau to fire AP.

A

Longer

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22
Q

What is ^?

A

Length constant

Depends on membrane resistance

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23
Q

Calculate ^

A

SQRT(membrane resistance) /

SQRT(intra r + extra r)

best passive current: lower intra/extra r and higher membrane resistance

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24
Q

Increase strength of depolarization: does this make bigger AP?

A

no, more AP but not bigger

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25
Q

Passive responses

A

below thershold

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26
Q

active response/conductance

A

above threshold

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27
Q

negative current

A

hyperpolarization

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28
Q

Rising phase

A

rapid depolarization

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29
Q

overshoot

A

positive to 0 mV

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30
Q

Falling phase

A

repolarization

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31
Q

undershoot

A

hyperpolarization following the spike

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32
Q

Voltage Clamp Technique

A

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 `

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33
Q

What happens in squid axon if you replace Na+ with choline?

A

only outward current now

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34
Q

Does K+ activate faster or slower than Na+?

A

Slower

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35
Q

Block Na+

A

TTX

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36
Q

Block K+

A

TEA

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37
Q

Steps of AP

A
  1. activate Na+ = Na+ ions into cell, depolarize, activates K+ channels
  2. Inactive Na+
  3. Hyperpolarize K+
  4. Na+ inactive portion removed
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38
Q

Patch clamp allows for

A

individual or small numbers of ion channels

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39
Q

Cell-attached recording

A

response of channels/channels pipette has covered

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40
Q

Whole-cell recording

A

more suction, membrane disrupted

electrode interior continuous with cell interior

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41
Q

Inside-out recording

A

intact membrane, suction away from cell

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42
Q

Outside-out recording

A

pull back some membrane, and have it reform such that cytoplasmic side frees electrode.

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43
Q

Na+ conductance

A
rapid onset (activation) 
rapid offset (inactivation)
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44
Q

K+ conductance

A

slow onset/offset

after hyperpolarization (undershoot)

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45
Q

Refractory period: absolute refractory period

A

Na+ channel inactivation

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46
Q

relative refractory period

A

afterhyperpolarization

higher threshold

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47
Q

If AP travels in both directions, what stops it from going back and forth?

A

refractory period

AP travels at specific rate.

48
Q

_______ measures the rate at which electrical impulses move along a nerve.

Used to diagnose disorders of the _______

A

nerve conduction study (NCS)

peripheral nerves and muscle

49
Q

Action Potential Propagation: Conduction of AP

A

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
Q

____ inactivation produces refractory period and prevents backpropagation

A

Na+

51
Q

______ repolarize membrane.

A

voltage-gated K+ currents

52
Q

Faster axons are

A

big and myelinated

53
Q

Why are larger axons faster?

A

less internal resistance

54
Q

Why myelin faster?

A

less capacitance
insulates axon
restriction to nodes of ranvier

55
Q

capacitive and ionic currents are highest at ____

A

nodes of Ranvier

56
Q

higher capacitance at unmyelinated nodes …

A

slows AP

57
Q

Loss of myelin means local circuits must charge…

A

larger areas, and reduce r means less change in V membrane.

58
Q

Structure of voltage gated channels

A
integral proteins 
may have several spanning domains
pore
voltage sensor - internal domain 
selective permeability
59
Q

What makes and maintains ion gradients?

A

ATPase PUMPS

60
Q

Channelopathies - small but critical alteration in ion channel gradients

Familial Hemiplegic Migraine (FHM)

A

migraine attacks the last 102 days, sever headaches vomiting

**Ca2+ Channel

61
Q

Channelopathies small but critical alteration in ion channel gradients

Episodic ataxia type 2 (EA2)

A

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
Q

Channelopathies small but critical alteration in ion channel gradients

X-linked congenital stationary night blindness (CSNB)

A

recessive retinal

night blindness, decrease acuity, myopia, nystagmus, strabismus, rod photoreceptors not functional

paralysis: decreased electrical excitability in muscles

**Ca2+ Channel

63
Q

Channelopathies small but critical alteration in ion channel gradients

Episodic ataxis type 1 (EA1)

A

brief episodes of ataxis (incoordination)

increased electrical excitability due to impaired AP repolarization

**K+ Channel

64
Q

Channelopathies small but critical alteration in ion channel gradients

Benign familial neonatal convulsion (BFNC)

A

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
Q

Generalized epilepsy with febrile seizures

A

increase Na+ influx and INCREASED electrical excitability in the brain

66
Q

Myotonia

A

increase Na+ influx and INCREASED electrical excitability and muscle stiffness (muscles)

DECREASE in Cl- conductance (muscles)

67
Q

Paralysis

A

decreased Na+ influx that causes DECREASE in electrical excitability (muscles)

68
Q

Paper: SCN9A channelopathy causes congenital inability to experience pain

A

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
Q

Electrical synapse characteristics

A

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
Q

Chemical synapse characterisitics

A

no direct contact, neurotranmitters in cleft

71
Q

Methionine Sulfoximine

A

inhibits glutamate synthesis (limit stroke damage)

72
Q

Carbidopa

A

inhibits dopamine synthesis (used in Parkinson’s)

73
Q
  1. How would you stop AP arriving at terminal?
A

Novacaine, Na+ channel blocker

74
Q

3-5. How do you stop depolarization and influx of Ca+ and vesicle stuff?

A

alpha latrotoxin- causes ca2+ independent transmitter release, convulsant

75
Q
  1. How do you block transmitter release?
A

Tetanus toxin, blocks GABA release, convulsant

76
Q
  1. Receptor binding interference
A

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
Q
  1. Example that stops reuptake
A

SSRIs, antidepressants

78
Q
  1. Degradation
A

cholinesterase, inhibitors, neostigmine

79
Q

Experimental setup: voltage clamp of presynaspe membrane: what did we learn about calcium and shit?

A

cadmium block and no EPSP.

SO calcium is needed for transmitter release

80
Q

SNARE:

Presyn

Postsyn

A

pre: SNAP25 and syntaxin
post: synaptobrevin

81
Q

Synaptotagmin

A

Ca2+ sensor

triggers membrane transmitter release

82
Q

Clostridium bactira
c. TETANUS
Botulism

A

PROTEASE. cleaves SNARE

block synaptic transmission

83
Q

Alpha-latrotoxin

A

binds to synaptotagmin causes calcium independent transmitter release

84
Q

Botulism

A

food bourne.
blurry vision, dry mouth, paralysis

fix with antitoxins

floppy baby

botox

85
Q

Tetanus

A

bacteria through puncture

blocks release of inhibitory NT, loss of inhibition on spinal motor neurons.

Descending pattern of symptoms

86
Q

Synthesis of DEN (Catecholamines)

A

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
Q

Reserpine

A

treats high blood pressure/psychosis
block catecholamine transmission

stops it getting in vesicles

88
Q

VMAT1

A

adrenal glands

89
Q

VMAT2

A

catecholamine and 5HT neurons

90
Q

3 ways of inactivation

A
  1. diffusion
  2. reuptake
  3. enzymatic inactivation
91
Q

MAO -A

A

affinity for NE and 5HT
inhibited by clorgyline
slow acting

92
Q

MAO -B

A

dopamine / o-phenylethlamine

inhibited by deprenyl (MPPP)

antidepressant, neuroprotective effects

Parkinson’s

sexual dysfunction

93
Q

COMT

A

inhibitors used to prevent inactivation of DOPA

94
Q

Tricyclic antidepressants target

A

NE

95
Q

Serotonin synthesis

A

Tyrptophan

Enzyme: Tryptophan hydroxylase (rate limiting)

5-hydroxytryptophan (5-HTP)

Enzyme: AADC

5-HT

96
Q

Serotonin facts

accumulated in vesicles by _____

inactivated by reuptake through ____

degraded by ____

Treaptuic effect slower, probably tied to downregulation of __________ on presynaptic membrane.

A

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
Q

JAMA on antidepressants

A

good if severe depression

98
Q

Histamine synthesis and facts

A

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
Q

gamma-aminobutyric acid (GABA)

A

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
Q

GABA receptor subtypes

A

A/C: ionotropic, increase Cl- conductance
B: metabotropic, increase K+ conductance

Benzo: antianxiety
Barb: hypnotics, anesthesia, epilepsy `

101
Q

Glutamate

A

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
Q

Acetylcholine

A

CAT makes it (Chat transfers acetyl to choline)
ACE degrades it

vesicles by VAChT

103
Q

Cholinesterase inhibitors

A

sarin, malathion, neostigmine

Block ACE, prolong Ach

104
Q

Ionotrophic

A

large, multisubunit
complex
fast onset/reversal

[N]
AMPA, Kainate, NMDA

105
Q

Metabotrophic receptors

A

single polypeptide
7 transmembrane domain
activated leads to binding and activating of G proteins

Slow onset/duration

[M]
beta-adrenergic

106
Q

[N]

A

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
Q

How are nACh [N] blocked?

A

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
Q

Metabolic G protein coupled receptors

A

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
Q

How are G proteins activated?

A

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
Q

G protein active state

A

beta and gamm

alpha-GTP

What turns off alpha subunit: GAP

E3 binds to alpha subunit

111
Q

G protein: when NT binds to receptor, ______ activates receptor

A

conformation change in i3 loop

112
Q

Over 1/2 of all prescription drugs work through

A

G ptrotein coupled receptors

113
Q

G protein couple receptors effects

A

ion channels cAMP/cGMP
intracellular enzymes
gene transcription

114
Q

Second messengers

A

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
Q

Excitation of skeletal muscle

A

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