Lecture 14 - bicarbonate

Question 1

Plasma HCO3 is approx

Answer 1

25mM

Question 2

how much fluid is filtered daily by kidney?

Answer 2

180L

Question 3

Amount of HCO3 filtered daily

Answer 3

approx. 4.5 moles

Question 4

Proximal tubule absorbs …% of HCO3

Answer 4

80%

Question 5

proximal tubule apical membrane

Answer 5

Na+/H+ co-transporter and H+ATPase with CAIV tethered

Question 6

Proximal tubule HCO3 reabsorption process

Answer 6

H+ secreted into lumen to combine with HCO3 to form H2CO3 in presence of H2CO3 by CAIV then splits into H2O and CO2
CO2 enters via apical membrane and combines with H2O by CAII to then break up to H+ and HCO3
HCO3 leaves the basolateral membrane via HCO3/Na cotransporter

Question 7

HCO3/Na co-transporter

Answer 7

can work in 1Na:3HCO3 or 1Na:2HCO3

Question 8

1:2 bicarbonate sodium cotransporter drives

Answer 8

drives UPTAKE into cell

Question 9

1:2 bicarbonate-sodium cotransporter drives

Answer 9

reabsorption of HCO3

Question 10

HCO3 reabsorption stimulation

Answer 10

angiotensin II, endothelia I, noradrenaline and adenosine, which is linked to calcium increases and PKC

Question 11

HCO3 reabsorption down regulated stimulated by

Answer 11

ANP, parathormone and dopamine, linked to cAMP/PKA pathway

Question 12

CO2 receptor control fo HCO3 absorption

Answer 12

level of blood CO2 acts to inhibit or stimulate

PT sense blood CO2 levels and alters HCO3 transport accordingly

Question 13

proximal tubule removal of HCO3

Answer 13

increased HCO3 reabsorption, though to maybe reduce back flux through tight junctions and increase exit gradients

Question 14

Proximal tubule removal of CO2

Answer 14

reduced HCO3 absorption, hypothesised CO2 receptor sensed blood CO2 levels

Question 15

Proximal tubule calcium channels

Answer 15

addition of HCO3/CO2 to lumen has no effect, but into the bath it increases calcium
Showed CO2 was responsible for calcium increase

Question 16

Inhibiting receptor protein kinases

Answer 16

abolished levels between CO2 levels and HCO3 transport

Question 17

protein tyrosine phosphatase Y location

Answer 17

proximal tubule basolateral membranes

Question 18

protein tyrosine phosphatase KO mice

Answer 18

fixed pH and HCO3 levels on basolateral but change CO2 which inhibited HCO3 transport
KO mouse does not respond to CO2
clamped CO2 and changed HCO3 to find KO insensitive to HCO3 levels

Question 19

protein tyrosine phosphatase Y hypothesis

Answer 19

when CO2 binds to phosphatase it causes inhibition of phosphatase activity therefore receptor protein kinases are upregulated/dominant

Question 20

HCO3 transport experiment

Answer 20

split-drop micro puncture techniques, introduced fluid drop into PT in between oil drops and measured droplet volume with time. Varied droplet composition and fluid in capillary perfusate, measure rate of change of droplet volume which is proportional to water permeability/flux across PT
Removal of HCO3 = rate of change goes down
Added DIDS = reduced water reabsorption
HCO3 absence = water reabsorption by PT is greatly reduced

Question 21

NHE3 KO mice

Answer 21

decreased BP, plasma pH and HCO3

Question 22

NHE3 conclusion

Answer 22

NHE3 drives 60% HCO3 reabsorption and 70% of H2O reabsorption in mouse PT
so H+ pump is not being unregulated for compensation

Question 23

pancreatic duct HCO3 secretion

Answer 23

CO2 enters cell, reacts with H2O to form H2CO3, splits to HCO3 and H+. HCO3 leaves cell via apical exchanger
H+ recycled across basolateral channel

Question 24

pancreatic duct apical membrane

Answer 24

Cl/HCO3 exchanger and CFTR

Question 25

Pancreatic duct basolateral membrane

Answer 25

Na/HCO3 cotransporter

H+/Na exchanger

Question 26

pancreatic duct luminal HCO3 conc increase

Answer 26

inhibits the anion exchanger and electrochemical gradients established favour continued HCO3 secretion

Question 27

SLC and CFTR resting conditions

Answer 27

both inactive, CFTR regulator domain interacts with nucleotide binding domains which inhibit channel action

Question 28

SLC and CFTR PKA stimulation

Answer 28

phosphorylation of CFTR regulatory domain and inhibition of CFTR is released and it acts as a HCO3 channel, also reacts with SLC regulatory domain to promote Cl/HCO3 exchange

Question 29

Pancreatic sufficiency is linked to…

Answer 29

ability of CFTR to transport HCO3