lecture 5/6 - redone

Question 1

sodium movement into the cell

Answer 1

enters through sodium channels down an electrochemical gradient by facilitated passive diffusion

Question 2

sodium movement out the cell

Answer 2

removed by Na/K ATPase which requires ATP, into the blood

Question 3

movement of chloride

Answer 3

chloride moves between the cells (paracellular diffusion) through tight junctions

Question 4

water follows the NaCl by

Answer 4

osmosis through aquaporins or tight junctions

Question 5

NKCC1 transporter transports

Answer 5

1 sodium
1 potassium
2 chloride
into the cell

Question 6

on the apical membrane the chloride channels we have are

Answer 6

CFTR and calcium activated chloride channels (CaCC)

Question 7

which part of the CFTR is phosphorylated by PKA and causes the channel to open

Answer 7

R domain

Question 8

CFTR activity is regulated by

Answer 8

PKA and ATP

Question 9

phosphorylation induces ATP binding to the

Answer 9

NBDs (nucleotide binding domains)

Question 10

then a conformational change in NBDs

Answer 10

transmits to MSD (membrane spanning domains) causing the pore to open

Question 11

ATP is hydrolysed and the pore

Answer 11

closes

Question 12

protein phosphatases

Answer 12

dephosphorylate of the R domain

Question 13

does the channel open if ATP is present but the R domain is not phosphorylated

Answer 13

no

Question 14

patch clamp technique allows you to

Answer 14

make electrical measurements of ions moving through ion channels
showed ATP alone had no response

Question 15

calcium activated chloride channels (CaCC) are activated by

Answer 15

a ride in calcium

Question 16

examples of CaCCs are

Answer 16

TMEM16A and B

Question 17

in TMEM16A what does the calcium bind to

Answer 17

glutamate residues in one of the alpha helices causing pore to open

Question 18

SLC26A anion exchanger brings chloride into the cell in exchange for

Answer 18

bicarbonate

Question 19

NBC (Na+ dependent HCO3- cotransporter) on basolateral membrane supplies

Answer 19

cytosolic HCO3- for the exchanger

Question 20

cAMP/PKA activation of CFTR does what to AE activity

Answer 20

switches it on

Question 21

what is required for CFTR to regulate the activity of AE (e.g SLC26A3)

Answer 21

interaction of the 2 channels by scaffold protein CAP70

Question 22

in CF, AE activity is

Answer 22

inhibited

Question 23

what 2 cells is the pancreas made up of

Answer 23

duct and acinar cells

Question 24

what do acinar cells secrete into the ducts

Answer 24

digestive enzymes and low volumes of NaCl rich fluid (using TEM16A (CaCC) channel)

Question 25

duct cells transport

Answer 25

digestive enzymes to SI produce a high volume of NaHCO3- rich solution using CFTR and SLC26A6 (AE)

Question 26

in CF what isnt secreted in the pancreas

Answer 26

NaHCO3- fluid (as CFTR and AE dont function)

Question 27

what does this cause

Answer 27

blockages in the ducts as the enzymes cant be solubilized

Question 28

why does the pancreas self digest

Answer 28

as the enzymes still get activates and start to degrade the pancreas

Question 29

role of ENaC in the kidney

Answer 29

sodium retention, controls body sodium and water balance and therefore blood pressure

Question 30

role of ENaC in the lungs

Answer 30

sodium and water absorption controls ASL

Question 31

role of ENaC in the colon

Answer 31

sodium and water reabsorption from the diet

Question 32

how many subunits does ENaC have

Answer 32

3 alpha, beta and gamma

Question 33

how many transmembrane domains does each subunit have

Answer 33

2 they form the pore of the channel

Question 34

inhibitor of ENaC

Answer 34

amiloride

Question 35

CAPs cleave the loops and

Answer 35

increase activity

Question 36

SLUNC1 binds to beta subunit and

Answer 36

inhibits ENaC

Question 37

where is ENaC expressed in the kidney

Answer 37

aldosterone-sensitive distal nephron (ASDN)

Question 38

renin is released in response to

Answer 38

low blood pressure

Question 39

renin converts angiotensinogen to

Answer 39

angiotensin I

Question 40

ACE 1 cleaves angiotensin I to

Answer 40

angiotensin II

Question 41

angiotensin II increases levels of

Answer 41

aldosterone

Question 42

aldosterone increases

Answer 42

sodium reabsorption through ENaC which increases extracellular fluid restores BP so renin stops being released

Question 43

aldosterone binds to cytosolic receptor and goes to nucleus to regulate transcription and translation of certain genes in order to increases

Answer 43

1. surface ENaC levels 2. Na/K ATPase density 3. ATP supply to support increased Na/K activity 4. K secretion across membrane

Question 44

aldosterone decreased rate of ______ for ENaC

Answer 44

retrieval

Question 45

retrieval of ENaC is regulated by ubiquitin ligase

Answer 45

Nedd4-2

Question 46

Nedd402 binds to

Answer 46

P-Y motif and adds ubiquitin group to a lysine residue signalling degradation of ENaC

Question 47

aldosterone stimulates production of

Answer 47

SGK1

Question 48

SGK1 phosphorylates Nedd4-2

Answer 48

prevents Nedd4-2 binding to ENaC inhibiting ubiquitination