Selectivity and Permeability

Question 1

1. Which region of ion channels determines selectivity and permeability?
2. What is selectivity and what is it determined by?
3. what is permeability and what is it determined by?

Answer 1

1. pore region
2. how easily an ion can enter the pote region; determined by Vrev
3. how easily an ion can move through the pore region once it has entered it; determined by current magnitude.

Question 2

1. where are the key amino acids that govern selectivity found in Na_v channels found?
2. how was the importance of certain residues for selectivity investigated?
3. what was the result of mutations in D1 and D2 pores?
4. what was the result of mutations in D3 and D4 pores?
5. What residues were found to be important in governing selectivity?

Answer 2

1. a number of amino acids in each domain
2. by mutating the second residue of each pore to a cysteine
3. a change in permeability
4. channels became calcium selective (change in selectivity)
5. 400, 755, 1237 and 1529, as well as additional residues in D4

Question 3

1. what is the signature sequence that governs selecitivty in K_v channels?
2. how was the importance of the signature sequence for selectivity tested?
3. in the study, under what conditions was Vrev measured. Therefore, what equation was used to determine the P_Na/P_K ratio?
4. what mutations were made at positions 1, 3 and 4. Why?
5. what mutations were made at position 7?
6. what does a Vrev of 0 and a PNa/PK ratio of 1 indicate?
7. what was the result of the mutations at positions 3 and 4?
8. what was the result of the mutatio at position 7?
9. Name 4 substitution mutations that produced a non-selective channel
10. what are the overall conclusions of this study?

Answer 3

1. TxxTGYG
2. by mutating certain residues within the siganture sequence
3. as a function of external [K], as Na was gradually substituted for K. Goldman Equation
4. substitution of threonine, to test the necessity of a hydroxyl group at these positions
5. subsitiution of tyrosine/phenylalanine, to test the neccessity of an aromatic ring at this position
6. that a channel is non-selective
7. a K+ selective channel was produced
8. a K+ selective channel was produced
9. T1G, V5A, G6C, and G8Q
10. the signature sequence underlies K+ selectivity.