Kir channel modulators

1. A method for identifying an agent that modulates an inwardly rectifying potassium channel activity, which comprises:

(a) inserting in silico a structure of an agent into a three-dimensional structure of an alcohol binding site of a Kir 2 or Kir 3 channel protein;

(b) comparing the fit of the agent in the three-dimensional structure with the fit of an alcohol in the three-dimensional structure, whereby an agent having a fit comparable to the fit of the alcohol is identified as a candidate agent that binds to a Kir 2 or Kir 3 channel protein;

(c) contacting a Kir 2 or Kir 3 channel protein with a candidate agent identified according to step (b); and

(d) detecting a Kir 2 or Kir 3 channel activity,

whereby an agent that alters the activity relative to a control activity determined without the agent is identified as an agent that modulates the inwardly rectifying potassium channel activity.

2. The method of claim 1 , wherein the Kir 2 or Kir 3 channel protein of step (a) lacks a transmembrane region.

3. The method of claim 1 , wherein the Kir 2 protein amino acid sequence of step (a) comprises the sequence of SEQ ID NO: 4.

4. The method of claim 1 , wherein the Kir channel protein of step (a) has a 90% or more identical amino acid sequence to SEQ ID NO: 4.

5. The method of claim 4 , wherein the Kir channel protein of step (a) lacks a transmembrane region.

6. The method of claim 1 , wherein the Kir channel protein of step (a) has a 90% or more identical amino acid sequence to SEQ ID NO: 8 or SEQ ID NO: 10.

7. The method of claim 6 , wherein the Kir channel protein of step (c) lacks a transmembrane region.

8. The method of claim 1 , wherein the Kir channel protein of step (c) comprises a Kir 3 protein amino acid sequence.

9. The method of claim 8 , wherein the Kir 3 protein amino acid sequence of step (c) comprises the sequence of SEQ ID NO: 8 or SEQ ID NO: 10.

10. The method of claim 1 , wherein the Kir 2 or Kir 3 channel protein of step (c) has one or more amino acids that are modified compared to the corresponding Kir 2 or Kir 3 channel protein of SEQ ID NO: 4, SEQ ID NO: 8, or SEQ ID NO: 10.

11. The method of claim 10 , wherein the Kir 2 or Kir 3 channel protein of step (c) lacks a transmembrane region.

12. The method of claim 10 , wherein one or more amino acids between amino acid position 1 to amino acid position 80 are modified.

13. The method of claim 10 , wherein one or more amino acids corresponding to Y58, I244, L257, L342, L344 and Y349 of Kir3.2 are modified.

14. The method of claim 10 , wherein one or more amino acids corresponding to F47, L232, L245, L339, E332, and Y227 of Kir 2.1 are modified.

15. The method of claim 14 , further comprising contacting the Kir 2 or Kir 3 channel protein with an alcohol.

16. The method of claim 15 , wherein the Kir 2 protein amino acid sequence contacted with the alcohol comprises the sequence of SEQ ID NO: 4.

17. The method of claim 15 , wherein the Kir 2 or Kir 3 channel protein contacted with the alcohol lacks a transmembrane region.

18. The method of claim 15 , wherein the Kir channel protein contacted with the alcohol has a 90% or more identical amino acid sequence to SEQ ID NO: 4.

19. The method of claim 18 , wherein the Kir channel protein contacted with the alcohol lacks a transmembrane region.

20. The method of claim 1 , wherein the Kir channel protein is in a cell.

21. The method of claim 1 , wherein the Kir channel protein is in a cell-free system.

22. The method of claim 1 , wherein the Kir channel protein, or the agent is in association with a solid phase.

23. The method of claim 1 , wherein the Kir channel protein comprises a detectable label.

24. The method of claim 1 , wherein the alcohol comprises a detectable label.

25. The method of claim 1 , wherein the Kir channel activity detected comprises binding of the Kir channel protein to the alcohol.

26. The method of claim 1 , wherein the Kir channel activity detected comprises membrane conductance.