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MSP Problem Set #8 1. PREDICT the RELATIVE permeabilities of the human red cell to the following compounds: [In the space available rank the predicted permeabilities from the highest (#1) to the lowest (#6)] a) CH2OHCH2CH2CH2CH2OH b) CH2OHCHOHCH2CH2CH3 c) CH2OHCH3 d) CH2OHCH2CH2CH2-O-CH3 e) H2O Provide the reasoning for your ranking. (The "correct" sequence may vary, depending on what assumptions you make about the red cell membrane.) 2. What are the key differences between: a.Transport of an ion through an Ion channel and through a Carrier. a. Cotransporters and Antiporters. c. Transport of ions across an epithelium through the Paracellular and Cellular pathways. 3. A new mutation in the CFTR gene (A559T) was recently identified in a group of cystic fibrosis patients living on Rathlin Island off the coast of Ireland. List three different mechanisms by which mutations in the CFTR gene might cause a defect in chloride transport across epithelial tissues in these patients. In order to investigate how the A559T CFTR mutation causes the defect in chloride transport, the researcher expressed both the wild-type and mutant genes in cultured cells (HEK293 cells) and measured the steady-state intracellular chloride concentrations and membrane potentials. She found the following values when the cells were incubated in media containing (in m-equiv/l): 145Na+, 4K+, 1Ca++, and 150Cl- buffered to pH 7.3. Control cells Intracellular [Cl-] mmol/kg H2O Membrane potential (mV) Transfected with wild-type CFTR Transfected with A559T CFTR 35 15 35 -60 -60 -60 4A. Given this information, what can you conclude about the chloride distribution between the incubation medium and i.control cells? ii.CFTR transfected cells? iii.A599T CFTR transfected cells? 4B.Given this information, what can you conclude about the defective CFTR channel. Bezanilla 5. The magnitude of the action potential (peak value minus resting potential) is about 100 mV. Compute how much charge is required to achieve this potential change in 1 cm2 of membrane. Compare this value with the experimental value of 5 pmole of Na net influx per impulse per cm2 and explain the difference. 6. If we stimulate an axon with a very slowly increasing current (instead of a pulse) we cannot produce an action potential. (Accommodation). Explain why. 7. If both the Na and K conductances increase with membrane depolarization, why is there first an inward current? 8. What do you have to change in the properties of the membrane to produce a plateau action potential? (plateau means that the depolarized state remains for a long period of time). 9. Why does the action potential of the squid axon show an undershoot? What would happen with the undershoot if the resting potential were equal to EK? 10. If the leakage conductance is very high, more stimulating current is required to initiate the action potential. Explain why. 11. Action potentials are initiated simultaneously at both ends of a long nerve fiber. Explain the events of propagation when the action potentials meet each other in the middle of the fiber. Do they 'pass' each other? 12. When the action potential activity is recorded with external electrodes during propagation the recorded event is in fact the longitudinal current. Do you expect to see the same signal when you record from one fiber as compared to many fibers simultaneously?