1. Transporters and Membranes By Sushil Pal Slides made using WMS transporters lecture, Molecules

2. Contents Transports – Types – Properties – Regulation – Function – Key examples (in my opinion) Membrane Potentials

3. Transport types?

4. Diffusion Passive Active Co-transport

5. Examples…. Diffusion PassiveGlucose transporter ActiveATPases (Ca++, Na+/K+, H+/K+) Co-transportSymporters (Na+/glucose, Na+/Cl-, Na+/HCO---) Antiporters (Na+/H+, Na+/Ca++)

6. Properties of Transporters Transporters are integral membrane proteins. Transporters are channels or carriers…. – What is the difference between these? Transporters are specific (or selective)… – What ways are they specific/selective? Transporters are regulated. Transporters are passive or active

7. The effect of Transporters on physiological processes…??

8. Uptake of metabolites. Extrusion of waste products. Maintenance of intracellular pH. Generation and use of ion gradients. Regulation of cell volume.

9. Transporter regulation…??

10. Voltage gated – membrane potentials Ligand gated – neurotransmitters – Ach Mechanically gated – sound, touch

11. Passive and Active transport differences…?

12. Passive – No metabolic energy use – Down a concentration gradient – Eg. Na+ entry into cells during AP Active – Metabolic energy use - ATP – Against a concentration gradient – Eg. H+ movement in electron transport chain

13. Important passive transporters.. 1)GLUT – Function: move and trap glucose into cells 2) Cl-/HCO3- anion exchanger – Function: regulate pH – Found in erythrocytes

14. Important Active Transporters Plasma membrane Ca 2+ -ATPase. Sarcoplasmic/endoplasmic reticulum Ca 2+ - ATPase – for 2ndary messengers Plasma membrane Na + :K + -ATPase Plasma membrane H + :K + -ATPase – parietal cells – acidic environment

15. Co Transporters Co-transport systems Symport AntiportUniport

16. Found in many locations to help different cellular functions Do you know any co-transporters..?

17. Na + symporters Glucose uptake (small intestine and kidney). Amino acid uptake (luminal epithelial cells). Cl - uptake (epithelial cells in small intestine). HCO 3 - uptake (regulates cell pH in many cell types). Na + antiporters H + export (regulates cell pH in most cell types). Ca 2+ export (muscle cells). Na + -dependent anion exchanger Na + & HCO 3 - influx and H + & Cl - efflux

18. Ion concentrations I recommend learning these..

19. Ion concentrations in a typical cell [K + ] 160 mM [K + ] 5 mM [Na + ] 10 mM [Na + ] 150 mM [Cl - ] 5 mM [Cl - ] 115 mM [Ca 2+ ] 0.2  M [Ca 2+ ] 2 mM [A - ] 165 mM [A - ] 40 mM Most organic molecules are negatively charged. - - - - - - - - + + + + + + + + Membrane potential = -70 mV

20. Nernst equation..simplified You should learn this too and know what the value means. – Your group work will run through more examples than your lecture Simplified Nernst equation at 37°C E ion 61 mV Z log [ion] out [ion] in =

21. Using the Nernst equation for K + at 37°C E ion 61 mV Z log [ion] out [ion] in = EKEK 61 mV 1 log 5 mM 160 mM = EKEK -91.8 mV= If [K + ] out increases to 10 mM (hyperkalaemia), E k is –73 mV. Can result in ventricular arrhythmia and fibrillation. Note: normal K+ con is 5mM outside the cells

22. Therefore an increase in extracellular K+ concentration will bring the membrane potential closer the threshold meaning the Action Potential will be easier to fire thus fibrillation and arrhythmias

23. Learn the action potential process!! Ie which channels are involved, what moves in and out etc It has come up in exams!!

24. Membrane potential Depolarisation is a decrease in membrane potential. Cytoplasmic side of the membrane becomes LESS negative ie close to 0 Opening Na + (or Ca 2+ ) channels depolarises cells. – Na + (and Ca 2+ ) ions flow into the cell. Hyperpolarisation is an increase in membrane potential. Cytoplasmic side of the membrane becomes MORE negative ie further from 0 Opening K + or Cl - channels hyperpolarises cells. – K + ions flow out of the cell, Cl - ions flow into the cell.

25. Refectory Periods.. Which types are they? Why are they important?

26. Refractory periods Membranes are refractory to stimulation during the action potential. This is the absolute refractory period. The membrane becomes more responsive as it repolarises. Very strong depolarisation produces a second action potential. This is the relative refractory period. +60 +20 0 -20 +40 -40 -60 -80 Membrane potential (mV) 12340 Time (ms) AbsoluteRelative refractory period

27. Learn all the different types of transporters and channels in your lectures. – As the year goes on you will come across them again and again so learning them in context will be more useful than in isolation. Getting you head around membrane potential is useful in Semester 2 Advice

28. Any questions??