week 19 epithelial fluid secretion Flashcards

1
Q

which has a greater fluid recover volume? small or large intestine

A

small 7L
Large 1.9L

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2
Q

what disease inhibits fluid reabsorption in the gut?

A

cholera

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3
Q

ion movement across a ‘tight’ epithelial monolayers drives _____ movement

A

water

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4
Q

polarised organisation of channels, pumps, exchangers and junction proteins determines _____ and ______ of water movement

A

direction and movement

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5
Q

how many routes of transepithelial water movement are there

A

2

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6
Q

intracellular movement of water occurs where

A

inside cells

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7
Q

intracellular movement of water occurs within cells and is regulated by what

A

water channels - aquaporins

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8
Q

paracellular movement of water occurs where

A

between cells

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9
Q

paracellular movement of water occurs between cells and is regulated by what

A

tight junction permeability

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10
Q

what are the 2 routes of transepithelial water movement

A

intracellular
paracellular

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11
Q

ENaC draws fluid from where of the cell nd into the blood

A

apical surface of the cell

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12
Q

what pump allows Cl- ions into the cell

A

NKCC

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13
Q

where is the NKCC pump located

A

on the basolateral surface of the cell

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14
Q

cl- accumulates in the ____ of the cell and creates ________ movement of which ion

A

lumen
paracellular movement
Na

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15
Q

Cl- channels = fluid _______

A

secretion

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16
Q

Cl- channels transport from where to where

A

basolateral to apical transport

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17
Q

Na+ channels = fluid _____

A

absorption

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18
Q

Na+ channels transport from where to where

A

apical to basolateral transport

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19
Q

what is the swelling-activated Cl- channel

A

(IClvol)

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20
Q

what does the swelling-activated Cl- channel (IClvol) do
how is it activated

A

activated transiently by osmotic shock
sustained opening does not occur

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21
Q

what is the calcium activated Cl- channel

A

CaCC

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22
Q

what does the Calcium activated Cl- channel do (CaCC)
how is it activated and is it transient?

A

activated by release of intracellular Ca2+ stores. Activity is transient and therefore unlikely to be sustained in development

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23
Q

what is the outwardly rectifying Cl- channel

A

(ORCC)

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24
Q

what does the Outwardly rectifying Cl- channel (ORCC) do
how is it regulated

A

regulated by release of intracellular ATP. Maintains potential by regulated depolarisation to physiological set point

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25
what is the cystic fibrosis transmembrane conductance regulator
CFTR
26
what does the cystic fibrosis transmembrane conductance regulator do what does it regulate and where
best characterised channel due to role in cystic fibrosis disease. Long presumed to be channel regulating fluid secretion in adult lung
27
what is the voltage dependant Cl- channel
CLCN
28
what does the voltage dependant Cl- channels (CLCN) do where is it and what process development does it follow (organ)
recently characterised in lung. Expression pattern follows the process of lung development
29
what is the CFTR a member of
member of the ATP binding cassette (ABS) glycoprotein superfamily
30
what is the kDa of CFTR
170kDa
31
how many _ transmembrane domains is CFTR composed of
2x 6 transmembrane domains
32
how many nucleotide binding domains does CFTR have
2
33
what are the 2 nucleotide binding domains that CFTR has (common to all ABC proteins)
NBD1 and NBD2
34
how many R domains are there in CFTR
1
35
what is a unique feature of CFTR
has one single domain of highly charged amino acids
36
in CFTR, the R domain is a regulatory site containing several ______ sites for what protein kinases
phosphorylation sites protein kinases A and C
37
activation of CGTR Cl- conductance requires ___ binding to what domains
ATP binding to the NBD domains and phosphorylation of the R domain
38
how many stages are there in the normal cycle of regulation of CFTR
6
39
STAGE 1 of normal cycle of regulation of CFTR what state is the channel in
channel is inactive
40
STAGE 2 of normal cycle of regulation of CFTR what does cAMP activate
cAMP activation of protein kinase A phosphorylates R domain
41
STAGE 3 of normal cycle of regulation of CFTR What does ATP bind to
ATP binds to NBD1 and NBD2
42
STAGE 4 of normal cycle of regulation of CFTR what is hydrolysed
ATP is hydrolysed
43
STAGE 5 of normal cycle of regulation of CFTR what happens to the channel what ion is conducted
channel opens and conducts Cl-
44
STAGE 6 of normal cycle of regulation of CFTR what happens to the R domain and subsequently the channel
dephosphorylation of the R domain inactivates the channel
45
what mutation in the NBD1 region of CFTR causes cystic fibrosis
Phenylalanine 508 (deltaF508 or F508del)
46
in delta508 CFTR (mutation that causes cystic fibrosis) what occurs
no fluid in the airway secretion - dry lung - sticky mucus - pathogen colonisation
47
In CLCN1-7 what is the channel opening gated by
membrane potential
48
IN CLCN1-7 where is it found
epithelia muscle nerve tissue plants
49
CLCN2 expressed in epithelium is activated at ______ cell membrane potentials
negative (hyperpolarised)
50
in CLCN 1-7 is composed of how many transmembrane domains
10
51
in CLCN1-7 the 10 transmembrane domains dimerise to form how many pores
2
52
in CLCN 1-7 the 10 transmembrane domains dimerise to form 2 pores, each pore is ________
voltage gated
53
CLCN1 mutation causes what
myotonia
54
in the CLCN1 mutation causing Myotonia - what does this cause
failure of muscles to relax after contraction as cells remain depolarised
55
what does a mutation in the CLCN5 mutation cause
Dent's disease
56
in the CLCN5 mutation causing dent's disease - what does this cause
fluid transport problems in kidney resulting in kidney stones, calcium and protein loss in urine
57
CLCN2 and CLCN3 are developmentally expressed in what foetal organ
lung
58
CLCN2 and CLCN3 are developmentally expressed in the feotal lung and control what
control lung fluid volume during development
59
where is the ENaC channel always found within epithelia
secretory epithelia lung, kidney gut, salivary duct, sweat duct
60
how many subunits is the ENaC composed of
3
61
what are the 3 subunits ENac composed of
alpha beta gamma
62
in ENaC a genetic alpha knockout results in what
lethal at birth due to flooding of the lungs
63
in ENaC knockout of beta or gamma subunits results in what
not lethal but is associated with a marked reduction in the rate of Na+ transport
64
in ENaC what is the dominant pore forming subunit
alphaENaC
65
ENaC is composed of alpha, beta, and gamma but how many subunits are there
4 2 alpha subunits
66
In ENaC what is the extracellular loop rich in
cystine
67
In ENaC within the extracellular loop what type of tertiary structure is it rich in
CSSC sulphur cross linking
68
what residue is involved in channel opening and closing within ENaC
histidine glycine residue
69
in ENaC what residue rich region serves as a binding motif for NEDD4
proline tyrosine
70
proline tyrosine residue rich region which srves as a binding motif for what
NEDD4
71
proline tyrosine residue rich region which srves as a binding motif for NEDD4 is what kind of ligase
ubiquitin ligase
72
proline tyrosine residue rich region which serves as a binding motif for NEDD4, a ubiquitin ligase which targets the subunit for membrane removal and what kind of degradation
proteolytic
73
what is ENaC inhibited by
amiloride
74
What is ENaC activated by
Beta2 adrenergic agonist
75
ENaC conductance is induced by what
catecholamines
76
pseudohypoalosteronism (PHA) and Liddle's syndrome are diseases associated with loss and gain of function mutations on what channel subunits
ENaC
77
PHA disease is associated with resistance to what hormone
aldosterone
78
As PHA is a disease associated with resistance to aldosterone what ion imbalance does this lead to
increased Na excretion - dehydration - hypotension -hyperkalaemia - metabolic acidosis
79
PHA disease is most evident in what organ
kidney
80
most lethal form of PHA is caused by loss of funtion mutations in what subunit in ENaC
alpha beta gamma
81
Liddle's syndrome is charcterised by what
hypertension hypokalaemia metabolic alkalosis repressed aldosterone secretion
82
results from gain of function mutations on what terminus domain if beta and gamma subunit in ENac
C terminal domain
83
In liddle's syndrone results from gain of function mutations in the C terminal domain of beta or gamma ENaC which result in the deletion of how many amino acids in the proline tyrosine rich PY domain
45-75 amino acids
84
results from gain of function mutations in the C terminal domain of beta or gamma ENaC which result in the deletion of how many amino acids in the deletion of 45-75 amino acids from what domain
proline-tyrosine rich PY domain
85
what ubiquitin ligase promotes internalisation and degradation of PY motif
NEDD4
86
channel activating proteases (CAP) increase what activity
ENaC
87
what increases ENaC activity
Channel Activating Proteases (CAP)
88
secreted CAP inhibitors block what and in what
secreted CAP inhibitors block CAP activity in concentrated ASL
89
how many extracellular CAPD are found in ASL
3
90
three extracellular CAPS dound in ASL can cleave what
ENaC
91
three extracellular CAPS found in ASL can cleave ENaC does what to its activity
increases the activity of ENaC
92
High ASL dilutes secreted what and secreted what
dilutes secreted protease inhibtors dilutes secreted CFTR agonists
93
Low ASL concentrates secreted CAP protease inhibitors and secreted _____ agonists
CFTR