Transporters and Channels 2 Flashcards
Transporters in facilitated diffusion
- hydrophobic, polar molecules can enter cell through specialised carrier proteins
- do not require energy
- can show saturation kinetics
Transporters in active transport
- hydrophilic, polar molecules can enter the cell through specialised carrier proteins
- requires energy
- is capable of moving molecules against concentration gradient
- can show saturation kinetics for carrier
What are P-glycoprotein transporters
- multidrug transmembrane transporters (ATP dependent)
- responsible for multi-drug resistance
Functions of P-glycoprotein transporters
- Liver: transporting drugs into bile for elimination
- Kidneys: pumping drugs into urine for excretion
- Placenta: transporting drugs into maternal blood
- Intestines: transporting drugs into intestinal lumen, reducing drug absorption into blood
- Brain capillaries: pumping drugs back into blood, limiting distribution in brain
Transport through symport
- solute A transport into cell is coupled with transport of solute B into cell
- CG going from area of lesser concentration to area of greater concentration, powered by movement of solute B going from high->low
Transport through antiport
solute A is transported against CG, powered by transporting solute B the opposite way (out)
Cis-effects of transporters
- saturability: substrate molecules compete for transporter binding-sites
- stereospecificity: certain stereoisomers are better fit to binding site
Trans-effects of transporters
- exchange diffusion: trans-substrate accelerates exchange
- counter transport: trans-acceleration by a different substrate (hetero-exchange)
Competitive inhibition
- increase substrate Km
- unchanged Vmax
Non-competitive inhibition
- decreased Vmax
- unchanged Km
How do Loop diuretics work
by blocking transport to sodium pump, leading to hypokalemia
How do thiazide diuretics work
- by blocking sodium chloride co-transporter, preventing sodium from entering pump and creating a gradient
- lowering Na concentration in epithelial cells increases activity in sodium potassium antiporter
Describe the mechanism of open channel blockers
- e.g. cocaine
- enter pore of ion channel or interact with intermediate stages involved in channel opening
- reduces frequency of APs occurring, results in a reduction in signal transmission
Structure of cys-loop receptors
- pentamers
- either homo-oligomers or hetero-oliogmers
- subunit composition affects pharmacology
Structure of ionotropic glutamate receptors
- tetramers
- either homo-oligomers or hetero-oligomers
- gated by glutamate and mediate excitatory neurotransmission in CNS
Structure of P2X receptors
- Trimers
- permeable to Na, K, and Ca, exceptionally Cl
- either homo-oligomeric or hetero-oligomeric
- 7 subunits identified
Structure of Acid-sensing (H+-gated) ion channels
- trimer
- conducts Na
- Three subunits identified (ASIC1-3)
- blocked by amiloride
- expressed in CNS and PNS -> modulate neuronal sensitivity to acidosis
- Related to epithelial Na channels (ENaC)
Where have ASICs been detected
- teste receptor cells
- photoreceptors
- lung epithelial cells
- urothelial cells
- adipose cells
- vascular smooth muscle cells
- immune cells
- bone
What are transporters/carriers
- selectivity related to molecular interaction between solute “substrate” and binding-site on carrier protein
- conformational change predicted
- carriage requires absorption of solute
- requirement for co-substrates
- exhibit counter-transport
What are channels
- selectivity related to size and charge of hydrated ion
- conformational change
- diffusoon single-file through narrow point of channel (saturable)
