Session 3 - Transporters, Ion Channels and Pores - Part 2

Question 1

Define primary active transport

Answer 1

Transport driven directly by the release of energy from the hydrolysis of ATP to ADP

Question 2

What is co-transport?

Answer 2

The movement of more than one molecule or ion via a single transport protein. Usual utilising the favourable movement of one molecule to for the unfavourable movement of another

Question 3

Define secondary active transport

Answer 3

Transport driven indirectly by the energy released by hydrolysis of ATP to ADP

Question 4

Give some examples of primary active transport proteins

Answer 4

PMCA (plasma membrane calcium ATPase) or SERCA (Sarcoplasmic reticulum calcium ATPase)

Na+/K+ ATPase

ATP synthase (reverse primary transport)

Question 5

Give some examples of some key co transport systems

Answer 5

3Na+/2K+ ATPase (anti port)
3Na+/1Ca2+ (anti port)
Na+/H+ (anti port)
Na+/glucose (symport)

Question 6

What happens in cystic fibrosis?

Answer 6

CFTR transporter is mutated and as such no longer exudes Cl- from the cell into the lumen. This reduces the movement of water into the lumen and the mucus becomes thick and viscous. The vpincreased viscosity of the mucus increases the likely hood of respiratory, GI, fertility and pancereatic problems (anywhere that mucus is secreted)

Question 7

How does cholera cause diarrhoea?

Answer 7

Bacteria like cholera activate protein kinase A which in turn activates the CFTR transporter as such more Cl- is exuded into the lumen of the GI tract which water follows and this results in very fluid stool.

Question 8

What are the main physiologically roles of the Na+/K+ transporter?

Answer 8

Necessary for electrical excitability
Drives secondary active transport
   - control of pH
   - regulation of cell volume
   - nutrient uptake

Question 9

Why is the control of Intracellular Ca2+ so important?

Answer 9

High Intracellular [Ca2+] is toxic to cells

Cells signal by small changes in Intracellular [Ca2+]

Question 10

What are the key proteins in the control of [Ca2+]?

Answer 10

Primarily NCX - 3Na+/Ca2+ exchange which removes most of the Ca2+

Then PMCA and SERCA - Ca2+/ H+ ATPase which have a high affinity but low capacity and remove the residual Ca2+ into the interstitial fluid and SER/ER respectively

Mitochondrial Ca2+ uniports -these operate at high concentrations and act to buffer the potential damaging effects

Question 11

What effect does the NCX transporter have on the cell when ischemic?

Answer 11

Ischemic - low blood flow to a tissue

1- low [O2] , ATP depleted so Na+/K+ pumped inhibited
2- [Na+] accumulates in cell and cell depolarises
3- NCX reverses
4- Na+ out is exchanged to bring Ca2+ in.
5- [Ca2+] increases in the cell and becomes toxic so damage occurs

Question 12

What mechanisms are send to control cellular pH?

Answer 12

Acid extruders:
NHE - Na+/H+ exchanger 
NBC - Na+ dependant Cl-/HCO3- (sodium coupled bicarbonate co-transporter)
Base extruders:
AE - CL-/HCO3- (anion exchanger)

Question 13

How do the transporters regulate pH?

Answer 13

Drop in pH (acidification):
NHE and NBC are activated

Increase in pH (alkylation)
AE activated

Question 14

How is cell volume regulated?

Answer 14

Movement of osmotically active ions via electro-neutral transport (ie. charges are balanced when moved) to maintain the cell membrane potential.

“Water follows ions”
Cell swells - exude ions and visa versa

Question 15

Why is almost all sodium and bicarbonate reabsorbed in the kidney?

Answer 15

Bicarbonate allows for the control of pH

Na+ allows for the control of hypertension

Question 16

How is Na+ re-absorbed in the proximal tube?

Answer 16

1-NHE (Na+/H+ exchanger) takes Na+ into tubule cell
2-Na+/K+ ATPase takes Na+ out of cell and into blood stream (K+ diffuses back into blood down it’s concentration gradient)

Question 17

How is bicarbonate reabsorbed in the proximal tube?

Answer 17

1- HCO3- bonds with H+ added via NHE and forms H2CO3
2- H2CO3 concerted to H2O and CO2 by carbonic anhydrase which then diffuses into the proximal tube cell
3- H2O and CO2 converted back to H2CO3 which desiccates back to H+ and HCO3-
4- H+ is used in transport of Na+ into the proximal tubule cell and the HCO3- exchanged into the blood for Cl- via the AE (anion exchange)

Question 18

How does amino ride act as a diuretic and as such a hypertensive drug? What are it’s side effects?

Answer 18

Amiloride inhibits the action of the NHE transporter and as such prevents the reabsorption of Na+ from the glomerula filtrate. This reduces the volume of water that returns into the blood and as such means more water is excreted in the urine. This reduces blood water and as such blood volume which in turn reduces blood?
However, the action of NHE extrudes H+ into the proximal tube to allow for HCO3- reabsorption so this is effected meaning that the buffering capacity of the blood is reduced

Question 19

What is an OAT and an OCT?

Answer 19

OAT = organic anion transporter
OCT = organic cation transporter