Revision 2: Membrane Permeability/Cell Volume and pH Regulation

Question 1

Types of transport

Answer 1

Active: allows transport against unfavourable conc. a/o elect. grad.s, requires ATP (some cells use 30-50% of ATP on this)

Diffusion: Dependant on perm. and conc. grad.s, rate of transport inc.s linearly w/ inc. conc. grad.

Can be passive -> no PM proteins needed, or facilitated -> inc. perm. to substance(s) w/ spec. prot.s in PM, models are ping-pong and prot. channels

Question 2

channel prot.s

Answer 2

can be gated - open/close in response to stim. eg ligand, ATP, change in V

>1 ion can be transported - known as co-transport - symport (1 directions) and antiport (>1 direction)

uniport is just one molecule

Question 3

free ion distribution across PM

Answer 3

all in mM

inside: Na: 12, Ca 0.0001, K 155, Cl 4.2
outside: Na: 145, Ca: 1.5, K: 4, Cl: 123

Question 4

outline major physiological roles of, and describe, Na/K-ATPase, K channels, Ca-ATPases, NCX

Answer 4

Na/K-ATPase: P type transporter - ATP phosphorylates aspartate, phosphoenz. intermed.s are made

• subunits: alpha - binding site for ATP, Na, K, ouabain, beta - glycoprotein directs pump to the surface
• Antiport - 3Na out, 2K in
• Role: forms the Na and K grad.s needed for electrical excitability and secondary transport (control of pH, cell volume, Ca conc. and absorption of Na in epith. and nutrients eg gluc. in SI)

K channels: K diffuses out, responsible for membrane potential of -70mV (approx.)

Ca ATPases antiports, 1 Ca out, 1 proton in, high aff. and low capacity so removes residual Ca: PMCA drives Ca out of the cell and H into the cell, SERCA drives Ca into the SER and H into the cell

NCX: 2^o transport, 1 Ca out, 3 Na in, low aff. and high capac. so removes most Ca, especially during cell recovery

-in ischaemia, the non functioning Na/K ATPase causes the pump to work the other way, Ca levels in cell rises -> TOXIC

Question 5

control of pH by ion transporters

Answer 5

NHE: acid extruder, 1 Na for 1 H, reg.s cell volume, activated by GFs and inhibited by amiloride

AE/Band 3: base extruder, 1 HCO₃ for 1 Cl, cell volume regulation

NBC: Acid efflux, base influx: 1 H and 1 Cl for 1 Na and 1 HCO₃

Question 6

control of cell volume

Answer 6

osmotically ‘active’ ions eg Na, K, Cl and organic osmolytes ie. AAs move I/O of cells, water follows, cell shrinks, swells

Question 7

drugs/hormones in kidney nephron

Answer 7

ADH: inc. aquaporins, inc. water reabsorption

Loop diuretics: blocks Na reuptake in thick ascending limb and proximal tubule, acts on Na/K/2Cl-transporter,

Amiloride: acts in dist/prox. convoluted tubule on ENaC/NHE, prevents Na reuptake, (also inhibits Na/K pump), also in collecting duct on ENaC

Aldosterone: inc. Na and water retention, upregulates aquaporins, ENaC, ROMK

spironolactone: glucocorticoid receptor antagonist, inhibits expression of aquaporins, ENaC, ROMK, Na/K-ATPase, cortical collecting duct, more water and Na loss, used if aldosterone is high

Question 8

corticol collecting duct transporters and drugs that work on them

Answer 8

transporters: aquaporins: water from duct to epith.
- ClC: Cl from duct all the way through to the lumen
- ROMK: K out of epith. to lumen/duct
- Na/K ATPase: Na into lumen, K into epith.
- ENaC: Na into epith from duct

Drugs: amiloride: inhibits ENaC, reducing Na reabsorption

Aldosterone: inc. Na and water retention, upregulates aquaporins, ROMK, ENaC

ADH: inc. aquaporins

spironolactone: inhibits Aquaporins and ENaC, more Na and water loss, generally given to counter high aldosterone levels