Lecture 6: Transporters, Ion Channels And Pores Part 3

Question 1

How does ion transport contribute to renal bicarbonate reabsorption?

Answer 1

• In proximal tubule cells, sodium hydrogen exchanger (NHE) drives out H+ and brings in Na+
• H+ and HCO3- forms H2CO3 using carbonic anhydrase and becomes H2O and CO2
• CO2 diffuses across the membrane into the proximal tubule cell
• CO2 reacts with water forming H2CO3 which dissociates into H+ and HCO3-
• Anion exchanger then transports HCO3- into the capillaries in exchange for Cl-
• This controls pH of the blood as a HCO3- acts as buffer

Question 2

How does ion transport contribute to renal Na+ handling?

Answer 2

• Na+ is reabsorbed by the proximal tubule cell using the sodium hydrogen exchanger in exchange for H+
• Na+ then gets transported into capillaries by Na+ K+ ATPase
• Renal Na+ handling is associated with handling hypertension
• Amiloride inhibits Na+ reupfake into proximal tubule, reduced Na+ re entering blood, reduces water uptake, blood volume, blood pressure

Question 3

How do organic anion transporters mediate the cellular uptake of organic anions?

Answer 3

• They take in organic anions from capillary in exchange of dicarboxylate ions via tertiary active transport (
• Organic anions then enters lumen via other channels

Question 4

How may renal OATs affect attained plasma drug levels?

Answer 4

• Regulate the entry of drugs into renal proximal tubules for renal excretion
• If OAT inhibited, renal clearance reduced, plasma level increased and negative side effects increased

Question 5

How do OATs contribute to inter organ and interorganismal communication?

Answer 5

They regulate levels of key metabolites and Signalling molecules in blood and in excretions, which helps interorgan and interorganismal communication (breast milk, volatile odorants in urine)

Question 6

How do OCTs mediate the cellular uptake of organic cations?

Answer 6

• OCT brings in OC+ to the proximal tubule cell, driven by electrochemical gradient (negative membrane potential)
• OC+ transport from proximal tubule cell to the lumen is done by multi drug and toxin extrusion proteins (MATE), which is driven by pH gradient (H+ goes into tubule cell)

Question 7

How may renal OCTs affect attained plasma drug levels?

Answer 7

• May affect drug availability - meteor in (anti diabetic drug) decreases hepatic glucose production, some patients have reduced activity of OCT1, so hepatic uptake of metformin reduced, reducing anti-diabetic effects

Question 8

How may OCTs enhance cytotoxicity of anti-cancer drugs and result in nephrotoxicity in parallel?

Answer 8

• May cause toxic drug accumulation - cisplatin excellent substrate for OCT2, readily taken into cells but is a poor substrate for MATE, reduces renal excretion, leading to toxic build up in proximal tubule cell, leading to nephrotoxicity