M&R Membrane structure and permeability

Question 1

What are the modes of facilitated diffusion?

Answer 1

• protein channels
• carrier proteins (ping pong)
• protein flip flop thermodynamically unlikely

Facilitated transport is saturable and there is a finite number of transport proteins

Question 2

What is the difference between primary and secondary active transport?

Answer 2

In active transport the unfavourable movement of the transported ion/molecule must be coupled to a thermodynamically favourable reaction.

Primary active transport: the energy comes from the direct hydrolysis of ATP

Secondary active transport: the energy comes from diminishing the concentration gradient of another molecule e.g. a co-transporter

Question 3

Define:
Uniport
Symport
Antiport

and state which are cotransporters.

Answer 3

Uniport: one molecule is transported from one side of the membrane to the other

Symport: one molecule is transported simultaneously with another molecule in the same direction

Antiport: one molecule is transported simultaneously with another molecule in the opposite direction

Symporters and antiporters are cotransporters

Question 4

What is the role of Na+ - K+ - ATPase?

Answer 4

Forms and maintains the Na+ and K+ gradients needed for electrical excitability

Drives secondary processes (due to the Na+ K+ gradient established:

• pH
• Cell volume
• ion gradients for resting membrane potential
• intracellular [Ca2+]

Question 5

How is intracellular [Ca2+] controlled?

Answer 5

Primary active transport:
–PMCA expels Ca2+ out of the cell, H+ into cell
High affinity so removes residual Ca2+

–SERCA accumulates Ca2+ in the SR, H+ out
High affinity so removes residual Ca2+

Secondary active transport:
–NCX removes most Ca2+ from cell, uses Na+ gradient

–Mitochondrial Ca2+ uniports buffer [Ca2+]

Question 6

Outline the role of NCX in the cardiac action potential and ischaemia.

Answer 6

NCX exchanges 3 sodium for 1 calcium
Role in cardiac AP:
In the depolarised cell NCX reverses so Ca2+ enters the cell during cardiac AP

Ischaemia:
ATP is depleted therefore the N+ - K+ ATPase is inhibited, so Na+ accumulates causing depolarisation. NCX reverses, so there is an influx of TOXIC calcium, causing further damage.

Question 7

How do ion transporters regulate cell pH?

Answer 7

Ion transporters used when cell buffering capacity is exceeded.

If cell becomes too acidic:
(NHE) Na+ - H+ exchange extrudes H+

If cell becomes too alkali:
(AE) anion exchange extrudes HCO3- in exchange for Cl-

Question 8

How do ion transporters regulate cell volume?

Answer 8

Transport must be electroneutral to prevent changing the membrane potential

Mechanisms to resist cell swelling:
Efflux osmotically active ions e.g. Na+ K+ Cl- so water follows

Mechanisms to resist cell shrinking:
Influx osmotically active ions e.g. Na+ K+ Cl- so water follows

Question 9

Outline bicarbonate reabsorption in the proximal tubule

Answer 9

The kidney reabsorbs all of the bicarbonate in the proximal tubule to retain base for pH buffers.

The sodium potassium pump keeps Na+ conc low in the proximal tubule cells so NHE can pump H+ ions into the proximal tubule lumen

H+ combines with bicarbonate in the lumen to bring it back into the cell.

Question 10

Outline renal anti-hypertensive therapy

Answer 10

Usually all Na+ reabsorbed
Renal anti-hypertensive therapy reduces the repute of sodium so less water is reabsorbed.
If less water is reabsorbed, blood volume and pressure fall.

Question 11

Outline the mechanism of diuretics and give examples

Answer 11

Loop diuretics block sodium reuptake in the thick ascending limb
eg Amiloride acts on proximal and distal convoluted tubules to block Na+ reuptake (inhibits NHE)

Aldosterone opposes diuretics by up-regulating the transporters.