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BMS2002 > strand 1 > Flashcards

strand 1 Flashcards

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1
Q

SCN9A

A

gene linked to human pain perception
mutations> channelopathies

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2
Q

secondary active transport

A

indirect coupling molecule with another moving along echem gradient
antiport/ symport

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3
Q

Na+-K+ ATPase

A

cytoplasmic Na+ binds
pump ATP-phosphorylated
conformation change (Na+ release)
extracel K+ binds (dephosphorylation)
pump returns to conformation (K+ release)

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4
Q

Na+-K+ ATPase ratio in and out

A

3 Na+ out
2 K+ in

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5
Q

experimental methods for ion channel investigation

A

patch-clamp electrophysiology (measure V change across PM)
(cryo) electron microscopy
X-ray crystallography

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6
Q

Vm

A

Vi-Vo

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7
Q

equilibrium potential

A

when ion flux in/out is balanced

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8
Q

Nernst equation

A

E ion= zF/RT ln( [ion] inside/[ion] outside)
simplified to > 61/z (log([ion]out/[ion]in)

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9
Q

shaker potassium channel

A

KCNQ1
Sh gene in drosophilia
a/b sub units
shorter lifespan and less sleep efficiency

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10
Q

closest human homologue of drosophilia Sh gene

A

KCNA3

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11
Q

gating types

A

ligand
voltage
mechanical

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12
Q

TTX

A

tetrodotoxin
blocks Na channels

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13
Q

ion channel structure investigation

A

amino acid structure> side chains predict structure
hydrophobic = transmembrane
hydrophilic = extramembrane

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14
Q

X-ray crystallography

A

crystallize, X-ray > e- density map > atomic model

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15
Q

positives of X-ray crystallography

A

any size molecule/ macromolecule

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16
Q

negatives of X-ray crystallography

A

may damage protein
may take years

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17
Q

cryo-electron microscopy

A

frozen in any state and microscopy

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18
Q

positives of cryo-electron microscopy

A

any size/ macro
near-atomic resolution
fastc

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19
Q

nuclear magnetic resonance

A

dissolved and radioactively labelled

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20
Q

negatives of nuclear magnetic resonance

A

larger molecules can’t be conserved

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21
Q

characteristics of ion channels difficult to crystallize

A

transmembrane
large
multi[ple conformations/ sub-units
dynamic and disordered
low solubility

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22
Q

alpha fold

A

future structure prediction of protein via databanks
:) rapid

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23
Q

no. homologue domains in K channel

A

4

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24
Q

Na+ trajectory/ elution

A

tortuous trajectory
slow elution

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25
K+ trajectory/ elution
straight trajectory fast passage
26
K channel selectivity filter
narrow selectivity filter mutations can abolish selectivity
27
N-type channel inactivation
amino acid N-terminus occlude intracellular side of pore rapid inactivation
28
C-type channel inactivation
hinged lid conformational change at selectivity filter/ extracel entrance slow inactivation
29
PETAFLOP
measurement unit for 10^16 complex operations per second
30
major extracellular ions
cations: K/Mg anions: phosphate/ amino acids
31
major intracellular ions
cations: Ca/ Na anions: Cl
32
RMP
-70mV maintained via K+ leak channels and ATPase pumps
33
Action potential
rid change in RMP sudden reverse in membrane polarity
34
stages of action potential
resting depolarisation (-70> +30 mV) repolarisation hyperpolarisation
35
v-gated channels
Na+ enters K+ leaves
36
Na+ gate threshold
-55mV fast opening v-gated automatic/ fast v-gated slow/ automatic inactivation from closed
37
K+ gate closure
slow opening/ closure
38
absolute refractory period
no AP generated Na+ channel inactivated
39
relative refractory period
AP generation w large stimulus Na+ channels recovered K+ channels still open
40
nociception
sensory nervous system's process of encoding potentially harmful stimuli. Mediated by ion channels
41
stimuli transduction
through nociceptors, transmitted up primary afferent nociceptor, modulated through interneurone, up spinothalamic tract into thalamus via thalamocortical projections then brain perception
42
nociceptor fibre types
A beta A delta C fibre
43
what do a beta fibres detect?
non-noxious mechanical stimuli
44
what do a delta fibres detect?
noxious mechanical stimuli
45
what do C fibres detect?
noxious heat and chemical stimuli
46
myelination of nociceptive fibres
a beta myelinated a delta lightly myelinated c is not myelinated
47
diameter of nociceptive fibres
a beta large a delta medium c is small
48
function of nociceptive fibres
a beta is proprioception a delta is nociception c is nociception
49
thermal threshold of nociceptive fibres
a beta has no thermal threshold a delta is ~53 (type I) /47 C (type II) c is ~43 C
50
transient receptor potential channels
ion channels responding to heat/acid/reactive chemicals/ enviro cold/ cold hyperalgesia additive effects
51
acute vs chronic pain
acute <3 months chronic > 3 months
52
pain classes
normal inflammatory neuropathic
53
somatic pain
peripheral nervous system specific localisation a delta and c fibres pain-relief response
54
visceral pain
viscera (uterus/ intestine/ kidneys/ stomach) non-specific region a delta and c fibres autonomic symptoms poor pain relief response
55
inflammatory pain
macrophage/ mast cell/ neutrophil/ granulocyte regulated treatment> COX2 inhibition localized pain and swelling persistent/ chronic nature
56
neuropathy
damage causing changes to expression/ post-trans mod of nociceptors not easily repaired v specialized opioid/ anticonvulsants/ Na+ channel blocker/ NMDA antagonist
57
pain relief targets
nociceptors NaV channels
58
pain relief issues w nociceptors
heterogeneous pain response >1 nociceptor redundancy side effects other tissue expression BBB non-permeable to drugs
59
NaV channel target
alpha sub-unit at VGSC at dorsal root ganglia enrichment or exclusive depression
60
lidocaine
reversible binding to inner pore of V-gated Na+ channels in open/ inactivated states greater affin for inactivated channels (not resting) non-selective
61
cystic fibrosis
mutation to CFTR gene Cl- influx dysfunction mucus accumulation and inflammation genetic linkage monogenic/ autosomal recessive 100% penetrance
62
class I CF mutation
no CFTR from mRNA
63
class II CF mutation
protein folding and trafficking failure
64
class III mutation
gating failure
65
class IV mutation
decreased stability at membrane
66
class V mutation
insufficient CFTR quantities
67
linkage mappong
mendelian inheritance pattern of single gene trait segregated trait in fam map SNP to locus
68
SCN9A gene voltage gate
1.7 NaV expressed by dorsal root ganglia sensory neurone contributes to rising phase amplifies subthreshold stimuli TTX responsive fast kinetics
69
paroxysmal extreme pain disorder
autosomal dominant severe pain in rectal/ ocular/ mandible chewing/ heat triggers childhood onset impaired inactivation
70
inherited erythromelalgia
autosomal dominant burning pain in hands and feet exercise/ heat triggers childhood onset enhanced activation
71
small fibre neuropathy
loss of function autosomal dominant
72
inherited erythromelalgia mutation
L858H mutation in 2nd domain lowers activation threshold therefore NaV1.7 open more readily to smaller depolarizations prolonged channel opening due to slow inactivation ^ramp response shift v-dependence of in/activation for ^hyperpolarized potential inactivation
73
PEDP mutation
decreases channel activation threshold delayed channel inactivation ^ response to repetitive stimulation
74
CIP
complete insensitivity to pain
75
complete insensitivity to pain
autosomal recessive complete sensation loss non-sense mutations in domains 1/11 premature stop codon > truncated protein
76
therapies for complete insensitivity to pain
small molecules mimicking toxin binding (belter PK/PD) botox *doesn't target NaV

BMS2002 (5 decks)

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