Session 2 Flashcards
Describe the ionic differences in composition between intracellular and extracellular fluids
Na+ - 145mM OUT, 12mM IN
Cl- - 116mM OUT, 4.2mM IN
Ca2+ - 1.5mM OUT, 200nM IN
K+ - 4mM OUT, 140mM IN
What are the roles of transport processes
Maintenance of ionic composition, maintenance of intracellular pH, regulation of cell volume, concentration of metabolic fuels and building blocks, removal of waste products, generation of ionic gradients
Discuss the principles of solute movement across biological membranes
Hydrophobic molecules (O2, CO2, N2, benzene) and small, uncharged polar molecules (H20, urea, glycerol) diffuse across easily. Large, uncharged polar molecules (glucose, sucrose) and ions (H+, Na+, K+, Ca2+, Mg2+, Cl-, HCO3-) do not diffuse across.
Distinguish passive diffusion, facilitated transport and active transport across membranes
Passive diffusion - dependent on permeability and concentration gradient, rate is proportional to concentration gradient
Facilitated transport - via protein pores, carrier molecules, ligand gated, voltage gated of gap junction
Active transport - allows the transport of ions or molecules against an unfavourable concentration and/or electrical gradient (energy directly or indirectly from ATP hydrolysis)
Define the terms uniport, co-transport, symport and antiport
Uniport - one substance is transported from one side of the membrane to the other
Co-transport - more then one type of ion or molecule is transported per reaction cycle
Symport - in the same direction
Antiport - in the opposite direction
Outline the major physiological roles of sodium-potassium ATPase (Na+-K+ ATPase, Na pump), plasma membrane Ca2+ ATPase (PMCA), sarcoendoplasmic reticulum ATPase (SERCA), sodium calcium exchange (NCX), sodium hydrogen exchange (NHE), anion exchange (AE)
Na+-K+ ATPase (primary active transporter):
P-type ATPase, 2 subunits (a - functional, B - directs pump to surface), forms Na+ and K+ gradients, generates gradient for other secondary active transporters (ion homeostasis, pH, cell volume), not primarily responsible for membrane potential, inhibited by Oubain
PMCA (primary active transporter):
Expels Ca2+ out of cell, high affinity, low capacity
SERCA (primary active transporter):
Accumulates Ca2+ into SR/ER, high affinity, low capacity
NCX (secondary active transporter):
Exchanges 3Na+ for 1Ca2+, role in expelling intracellular Ca2+, low affinity, high capacity
NHE:
Exchanges extracellular Na+ for intracellular H+, regulates pH, cell volume, activated by growth factors, inhibited by Amiloride
AE:
Cl-/HCO3- exchanger, base extruder - acidifies inside of cell
Discuss how ion transporters work together in cell physiology
Cystic fibrosis:
Cl- enters via Na+/2Cl-/K+ symport, accumulates in cell due to faulty CFTR protein –> lack of osmotic gradient leads to retention of water in cell –> viscous mucus
Diarrhoea in cholera:
Cholera toxin stimulates protein kinase A which increases activity of CFTR, more water leaves cell due to increased osmotic gradient –> diarrhoea
Ischaemia:
NCX expels Ca2+ during cell recovery. When membrane is depolarised, NCX reversed. In ischaemia, ATP is depleted - Na+ pump inhibited. Na+ accumulates in cell –> membrane depolarisation. NCX reverses and Ca2+ accumulates in cell –> toxicity
Discuss how ion transport contributes to control of resting intracellular Ca2+
Intracellular Ca2+ needs to be controlled to prevent calcium toxicity (stimulates other things in cell, insoluble calcium phosphate crystals)
Primary active transport:
PMCA, SERCA
Secondary active transport:
NCX
Facilitated transport:
Mitochondrial Ca2+ uniports buffer dangerous levels of Ca2+
Discuss how ion transport contributes to control of cellular pH and cell volume regulation.
Cellular pH:
pH is held at a set point by different pumps
Acid extruders (alkalinisation) - NHE, NBC (sodium bicarbonate cotransporter)
Base extruders (acidification) - AE
Cellular volume:
Transport of osmotically active ions creates an osmotic gradient. Water follows the gradient –> cell shrinkage/swelling
NHE, NBC, AD
Discuss how ion transport contributes to control of renal bicarbonate reabsorption and renal Na+ handling
All bicarbonate is reabsorbed by kidneys. Carbonic anhydrase enables H2CO3 H20 + CO2
Renal Anti-Hypertensive Therapy
Thick ascending limb - loop diuretics inhibit NKCC2
Distal convoluted tubule - thiazides inhibit NCCT, Amiloride inhibits Enac
Cortical collecting duct - Amiloride inhibits Enac, spironolactone is an antagonist of aldosterone receptor
