lecture 25 - chloride secretion

Question 1

NaK2Cl symporter transports? (where is it found)

Answer 1

1 Na+, 1 K+ and 2 Cl- into the cell from the basolateral membrane.

Question 2

once they have entered into the cell, through the NaK2Cl symporter, what is the fate of the Na+, K+ and Cl- ?

Answer 2

• Na+ pumped out via basolateral Na pump - K+ exits via channel in the basolateral membrane - Cl- leaves via passive diffusion through CFTR ion channel

Question 3

transcellular transport of Cl- across the epithelium induces?

Answer 3

Na+ and water fluxes

Question 4

in chloride secretion, how does the permeability of tight junctions differ to that of glucose absorption?

Answer 4

in chloride secretion they are more permeable to Na+, whereas they are more permeable to Cl- in glucose absorption.

Question 5

what is the rate limiting step of Cl- secretion

Answer 5

Cl- leaving the cell through CFTR ion channel. Cl- is accumulated well above its electrochemical gradient but opening of this channel is strictly regulated and Cl- can’t leave any other way.

Question 6

chemical that initiates Cl- secretion

Answer 6

secretogogues

Question 7

CFTR stands for… does everyone have it or nah?

Answer 7

Cystic Fibrosis transmembrane conductance regulator. Cl- ion channel. yeah g, everyone has it

Question 8

CFTR overstimulation leads to

Answer 8

diarrhoea

Question 9

CFTR dysfunction =

Answer 9

cystic fibrosis

Question 10

secretory diarrhoea is associated with secretory cells in the _____ of the ____ ______ and ______.

Answer 10

secretory diarrhoea is associated with secretory cells in the _crypts_ of the _small_ _intestine_ and _colon_.

Question 11

secretory diarrhoea less common cause =

Answer 11

higher than normal concentrations of endogenous secretogogues produced by tumours or inflammation

Question 12

More common cause of secretory diarrhoea =

Answer 12

ENTEROTOXINS secreted by CHOLERA and other bacteria cause an overstimulation of CFTR

Question 13

_______ (ligand) binds and activates the _ ______ which moves along the ________ membrane to activate the ______ ______. This enzyme can then convert ATP to ____, which goes on to activate _____ _____ _, in turn phosphorylating _____ (found in the _____ membrane) - the channel is now open. Once the ligand unbinds the gate _____.

Answer 13

_secretogogues_ (ligand) bind and activate the _G_ _protein_ which moves along the _basolateral_ membrane to activate the _adenylate_ _cyclase_. This enzyme can then convert ATP to _cAMP_, which goes on to activate _protein_ _kinase_ _A_, in turn phosphorylating _CFTR_ (found in the _apical_ membrane) - the channel is now open. Once the ligand unbinds the gate _closes_.

Question 14

how does Cholera affect the control over opening/closing of CFTR gate?

Answer 14

IRREVERSIBLY activates adenylate cyclase which will keep CFTR open.

Question 15

how will Cholera kill you?

Answer 15

Cl- continuously accumulates in the lumen, therefore there is extreme water loss - up to 20Kg

Question 16

treatment for over-secretion

Answer 16

“oral rehydration therapy” - counter-acted glucose/Na stimulated water flux.

Question 17

How do you cop Cystic fibrosis?

Answer 17

inherited from two heterozygous parents

Question 18

cystic fibrosis most prevalent in?

Answer 18

Northern Europe. Children and young adults are most affected.

Question 19

mean survival with cystic fibrosis?

Answer 19

38 years

Question 20

which tissues does cystic fibrosis largely affect

Answer 20

epithelial

Question 21

CF symptoms in liver

Answer 21

function disrupted and plugs bile ducts

Question 22

CF symptoms in pancreas

Answer 22

ducts block, so digestive enzymes cannot be delivered

Question 23

CF symptoms in small intestine

Answer 23

thick stool - constipation

Question 24

CF symptoms reproductive tract

Answer 24

infertile males - sperm production, but not enough ejaculate. Mucus in females may block sperm from egg.

Question 25

treatment of CF

Answer 25

• chest percussion - antibiotics for infection - Pancreatic enzyme replacement - attention to nutritional status

Question 26

Healthy sweat production

Answer 26

1. primary secretion of isotonic fluid by acinar cells 2. secondary reabsorption of NaCl, producing a hypotonic solution

Question 27

sweat production in cystic fibrosis patients

Answer 27

initial isotonic secretion by acinar cells, however, epithelial cells in sweat glands fail to reabsorb NaCl = salty sweat.

Question 28

is CFTR an ion channel or a pump?

Answer 28

ion channel i.e. water filled pore

Question 29

movement of Cl- through pore is regulated by which 3 cytoplasmic domains?

Answer 29

2 Nucleotide binding domains and 1 regulatory domain

Question 30

what must occur before the channel can open. How does it close again

Answer 30

1. The regulatory (R) domain must first be phosphorylated (regulated by protein kinase A) 2. ATP binds to each nucleotide binding domain = gate OPEN 3. gate closes when ATP is hydrolysed

Question 31

in a healthy brother, how is the lung surface kept moist

Answer 31

balance between Cl- secretion and Na+ absorption

Question 32

lung surface in CF patient

Answer 32

• dry (no isotonic secretion) - thick and sticky mucus secreted - cilia can’t sweep - WBCs build up in mucus - break down lung tissue = less surface area for gas exchange. - most deaths in CF result from this