Claims
- 1. An isolated polynucleotide that encodes a human β1A sodium channel subunit protein, said polynucleotide comprising a member selected from a group consisting of:
(a) a polynucleotide having at least a 75% identity to a polynucleotide encoding a polypeptide consisting of amino acids 1 to 268 of SEQ.ID.NO.:14; (b) a polynucleotide having at least 75% identity to a polynucleotide encoding a polypeptide consisting of amino acids 150 to 268 of SEQ.ID.NO.:14; (c) a polynucleotide which is complementary to the polynucleotide of (a) or (b); and (d) a polynucleotide comprising at least 15 sequential bases of the polynucleotide of (a), (b), or (c).
- 2. The polynucleotide of claim I wherein the polynucleotide is RNA.
- 3. The polynucleotide of claim 1 wherein the polynucleotide is DNA.
- 4. The polynucleotide of claim 1, having a nucleotide sequence selected from a group consisting of: (SEQ.ID.NO.:12) and (SEQ.ID.NO.:13)
- 5. The polynucleotide of claim 4 further consisting of allelic variants, mutants, and functional derivatives (SEQ.ID.NO.:12) and (SEQ.ID.NO.:13).
- 6. The polynucleotide of claim 1, wherein said DNA molecule is genomic DNA.
- 7. An expression vector for expression of a human β1A sodium channel subunit protein in a recombinant host, wherein said vector contains a recombinant gene encoding a human β1A sodium channel subunit protein and functional derivatives thereof.
- 8. The expression vector of claim 7, wherein the expression vector contains a cloned gene encoding a Human β1A sodium channel subunit protein, having a nucleotide sequence selected from a group consisting of: (SEQ.ID.NO.:12) and (SEQ.ID.NO.:13).
- 9. The expression vector of claim 8, wherein the group further consists of allelic variants, mutants, and functional derivatives of SEQ.ID.NO.:12 and SEQ.ID.NO.:13.
- 10. The expression vector of claim 7, wherein the expression vector contains genomic DNA encoding a Human β1A sodium channel subunit protein.
- 11. A recombinant host cell containing a recombinantly cloned gene encoding Human β1A sodium channel subunit protein or a functional derivative thereof.
- 12. The recombinant host cell of claim 11, wherein said gene has a nucleotide sequence selected from a group consisting of: (SEQ.ID.NO.:12); (SEQ.ID.NO.:13); and functional derivatives thereof.
- 13. The recombinant host cell of claim 11, wherein said cloned gene is genomic DNA.
- 14. An isolated protein encoded by a nucleic acid sequence capable of hybridizing under stringent hybridization conditions to a nucleotide sequence having the sequence of SEQ ID NO:12 or SEQ ID NO:13 that when combined with a Human α sodium channel subunit protein in a cell permits sodium ion flux in the cell.
- 15. The protein according to claim 14, having an amino acid sequence selected from a group consisting of: (SEQ.ID.NO.:14) and functional derivatives thereof.
- 16. A monospecific antibody immunologically reactive with a human β1A sodium channel subunit protein.
- 17. A process for expression of a Human β1A sodium channel subunit protein in a recombinant host cell, comprising:
(a) introducing an expression vector comprising a nucleic acid sequence capable of hybridizing under stringent hybridization conditions to a nucleotide sequence, or its complementary sequence, having the sequence of SEQ ID NO:12 or SEQ ID NO:13 into a cell; (b) culturing the cell of step (a) under conditions which allow expression of a a protein encoded by the nucleotide seuqence.
- 18. A method of screening for a modulator of sodium channel activity comprising:
(a) providing a cell that co-expresses a protein encoded by a nucleic acid capable of hybridizing under stringent hybridization conditions to a nucleotide sequence, or its complementary sequence, represented by SEQ ID NO: 12 or SEQ ID NO: 13 and a sodium channel α subunit protein wherein the cell elicits a sodium ion flux; (b) contacting the cell with a putative β1A modulating compound; and (c) measuring a change upon the cell that alters the sodium ion flux.
- 19. The method of claim 18 wherein at least one of the proteins is a recombinant protein.
- 20. The method of claim 18 wherein the change in sodium ion flux is selected from a group consisting of:
(a) increasing the capacity to open the Na channel; (b) decreasing the capacity to open the Na channel; (c) increasing the rate of desensitization; (d) decreasing the rate of desensitization; (e) increasing the rate of re-sensitization of the channel; (f) decreasing the rate of re-sensitization of the channel; (g) increasing the level of β1A protein expression; (h) decreasing the level of β1A protein expression; (i) increasing the level of the α/β1A complex protein expression; and (j) decreasing the level of the α/β1A complex protein expression.
- 21. A compound that modulates the function of human β1A selected using the method of claim 18.
- 22. A pharmaceutical composition comprising a compound of claim 19.
- 23. A method of treating neuropathic pain in a patient in need of such treatment comprising administration of a modulating compound of claim 21.
- 24. A method of treating neuropathic pain in a patient in need of such treatment comprising altering the level of a human β1A subunit in a dorsal root ganglia cell in the patient.
- 25. A method of treating chronic pain in a patient in need of such treatment comprising administering the compound of claim 21.
- 26. A method of treating febrile seizures in a patient in need of such treatment comprising administering the compound of claim 21.
- 27. A method of treating general epilepsy in a patient in need of such treatment comprising administering the compound of claim 21.
- 28. An anticonvulsant pharmaceutical composition comprising a compound of claim 21.
- 29. A method of treating arrhythmia in a patient in need of such treatment comprising administering the compound of claim 21.
- 31. A pharmaceutical composition comprising a compound of claim useful for use as a local anesthetic.
- 32. A method for decreasing neuropathic pain in an individual comprising administering to said individual a modulator of a sodium channel β1A subunit in an amount effective to change the sodium channel activity in said individual.
- 33. The method of claim 31 wherein said modulator decreases the expression of sodium channel β1A subunit in the cells of said individual.
- 34. A method for treating neuropathic pain in a subject comprising altering the level of sodium channel β1A subunits on the surface of a cell in a subject.
- 35. A method for decreasing neuropathic pain in a human comprising the step of administering a sodium channel β1A subunit-binding molecule to a sodium channel β1A subunit-expressing cell in the human.
BACKGROUND OF THE INVENTION
[0001] This case claims priority to U.S. Provisional Patent Application No. 60/294,405 filed Jun. 7, 2000 and entitled “DNA Encoding Human Voltage Gated Sodium Channel β1A Subunit” and U.S. Provisional Patent Application No. 60/236,664 filed Sep. 29, 2000 and entitled “DNA Encoding Human Voltage Gated Sodium Channel β1A Subunit.”
Provisional Applications (1)
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Number |
Date |
Country |
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60294405 |
Jun 2000 |
US |