Human KCNQ5 potassium channel, methods and compositions thereof

Abstract

An isolated polynucleotide encoding a novel potassium channel polypeptide, KCNQ5, that is expressed primarily in brain and skeletal muscle is described. The new polypeptide has been cloned and isolated from a human brain cDNA library and is a member the KCNQ family of potassium channels. The provided human KCNQ5 nucleic acid sequence and encoded polypeptide can be employed for diagnostic, screening and therapeutic uses. Moreover, the hKCNQ5 polypeptide can be used to assay for KCNQ5 potassium channel modulators, which can be utilized in the treatment of neurological, neurophysiological, neuropsychological and neuroaffective diseases, conditions and disorders, including, but not limited to, acute and chronic pain, migraine, acute stroke, dementia, vascular dementia, trauma, epilepsy, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, learning and cognitive disorders, and neurophysiological disorders including anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, and eating disorders.

1 - 24 . (Canceled)  
     
     
         25 . An isolated KCNQ5 polypeptide comprising all or a portion of the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         26 - 27 . (Canceled)  
     
     
         28 . A method of identifying a compound that modulates the biological activity of a KCNQ5 potassium channel polypeptide, comprising: 
 (a) combining a candidate modulator compound with a KCNQ5 potassium channel polypeptide having the sequence set forth in SEQ ID NO:2; and    (b) measuring an effect of the candidate modulator compound on the activity of the KCNQ5 potassium channel polypeptide.    
     
     
         29 . A method of identifying a compound that modulates the biological activity of a KCNQ5 potassium channel polypeptide, comprising: 
 (a) combining a candidate modulator compound with a host cell expressing a KCNQ5 potassium channel polypeptide having the sequence as set forth in SEQ ID NO:2; and    (b) measuring an effect of the candidate modulator compound on the activity of the expressed KCNQ5 potassium channel polypeptide.    
     
     
         30 - 31 . (Canceled)  
     
     
         32 . A compound that modulates the biological activity of human KCNQ5 potassium channel polypeptide as identified by the method according to  claim 28 .  
     
     
         33 . A compound that modulates the biological activity of human KCNQ5 potassium channel polypeptide as identified by the method according to  claim 29 .  
     
     
         34 . A compound that modulates the biological activity of human KCNQ5 potassium channel polypeptide as identified by the method according to claim  30 .  
     
     
         35 . A compound that modulates the biological activity of human KCNQ5 potassium channel polypeptide as identified by the method according to claim  31 .  
     
     
         36 . An antisense nucleic acid molecule which binds to the polynucleotide molecule according to claim  1 .  
     
     
         37 . An antisense nucleic acid molecule which binds to the polynucleotide molecule according to claim  2 .  
     
     
         38 . An antisense nucleic acid molecule which binds to the polynucleotide molecule according to claim  3 .  
     
     
         39 . (Canceled)  
     
     
         40 . A pharmaceutical composition comprising the polypeptide according to  claim 25  and a physiologically acceptable carrier, excipient, or diluent.  
     
     
         41 . A pharmaceutical composition comprising the polypeptide according to claim  26  and a physiologically acceptable carrier, excipient, or diluent.  
     
     
         42 . A pharmaceutical composition comprising the polypeptide according to claim  27  and a physiologically acceptable carrier, excipient, or diluent.  
     
     
         43 . A method for the production of a pharmaceutical composition comprising the steps of the method according to  claim 28  and further including step (c): formulating the compound that is capable of modulating the biological activity of the KCNQ5 polypeptide in a pharmaceutically acceptable form.  
     
     
         44 . A method for the production of a pharmaceutical composition comprising the steps of the method according to  claim 29  and further including step (c): formulating the compound that is capable of modulating the biological activity of the KCNQ5 polypeptide in a pharmaceutically acceptable form.  
     
     
         45 . A method for the production of a pharmaceutical composition comprising the steps of the method according to claim  30  and further including step (c): formulating the compound that is capable of modulating the biological activity of the KCNQ5 polypeptide in a pharmaceutically acceptable form.  
     
     
         46 . A method for the production of a pharmaceutical composition comprising the steps of the method according to claim  31  and further including step (e): formulating the compound that is capable of modulating the biological activity of the KCNQ5 polypeptide in a pharmaceutically acceptable form.  
     
     
         47 . The method according to  claim 43 , wherein the pharmaceutical composition is for the treatment of acute and chronic pain, migraine headache, acute stroke, dementia, trauma, epilepsy, seizure, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, eating disorders, ataxia, myokymia, Alzheimer's disease, age-associated memory loss, learning deficiencies, cognitive disorders, and motor neuron diseases.  
     
     
         48 . The method according to  claim 44 , wherein the pharmaceutical composition is for the treatment of acute and chronic pain, migraine headache, acute stroke, dementia, trauma, epilepsy, seizure, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, eating disorders, ataxia, myokymia, Alzheimer's disease, age-associated memory loss, learning deficiencies, cognitive disorders, and motor neuron diseases.  
     
     
         49 . The method according to  claim 45 , wherein the pharmaceutical composition is for the treatment of acute and chronic pain, migraine headache, acute stroke, dementia, trauma, epilepsy, seizure, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, eating disorders, ataxia, myokymia, Alzheimer's disease, age-associated memory loss, learning deficiencies, cognitive disorders, and motor neuron diseases.  
     
     
         50 . The method according to  claim 46 , wherein the pharmaceutical composition is for the treatment of acute and chronic pain, migraine headache, acute stroke, dementia, trauma, epilepsy, seizure, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, eating disorders, ataxia, myokymia, Alzheimer's disease, age-associated memory loss, learning deficiencies, and motor neuron diseases.  
     
     
         51 . An antibody specific for the KCNQ5 polypeptide according to  claim 25 .  
     
     
         52 . An antibody specific for the KCNQ5 polypeptide according to claim  26 .  
     
     
         53 . An antibody specific for the KCNQ5 polypeptide according to claim  27 .  
     
     
         54 . The antibody according to  claim 51 , wherein the antibody is a monoclonal antibody.  
     
     
         55 . The antibody according to  claim 52 , wherein the antibody is a monoclonal antibody.  
     
     
         56 . The antibody according to  claim 53 , wherein the antibody is a monoclonal antibody.  
     
     
         57 - 60 . (Canceled)  
     
     
         61 . A method for screening a plurality of compounds to assess specific binding affinity with a KCNQ5 potassium channel polypeptide, or a bindable portion thereof, comprising: 
 (a) providing a plurality of test compounds;    (b) combining the KCNQ5 polypeptide, or a bindable fragment thereof, with each of the plurality of compounds for a time sufficient to allow binding under suitable conditions; and    (c) detecting binding of the KCNQ5 polypeptide to each of the plurality of test compounds, thereby identifying the compounds that specifically bind to the KCNQ5 polypeptide.    
     
     
         62 - 63 . (Canceled)  
     
     
         64 . A method of screening for or detecting candidate compounds capable of binding to human KCNQ5 potassium channel polypeptide, comprising: 
 a) contacting a test compound with a purified KCNQ5 polypeptide according to  claim 25;  and    b) selecting as candidate compounds those test compounds that bind to the polypeptide.    
     
     
         65 . A method of screening for or detecting candidate compounds capable of binding to human KCNQ5 potassium channel polypeptide, comprising: 
 a) contacting a test compound with a purified KCNQ5 polypeptide according to claim  26 ; and    b) selecting as candidate compounds those test compounds that bind to the polypeptide.    
     
     
         66 . A method of screening for or detecting candidate compounds capable of binding to human KCNQ5 potassium channel polypeptide, comprising: 
 a) contacting a test compound with a purified KCNQ5 polypeptide according to claim  27 ; and    b) selecting as candidate compounds those test compounds that bind to the polypeptide.    
     
     
         67 . The method according to  claim 64 , wherein the polypeptide is immobilized onto a solid support.  
     
     
         68 . The method according to  claim 65 , wherein the polypeptide is immobilized onto a solid support.  
     
     
         69 . The method according to  claim 66 , wherein the polypeptide is immobilized onto a solid support.  
     
     
         70 . The method according to  claim 64 , wherein the candidate compounds are immobilized onto a support.  
     
     
         71 . The method according to  claim 65 , wherein the candidate compounds are immobilized onto a support.  
     
     
         72 . The method according to  claim 66 , wherein the candidate compounds are immobilized onto a support.  
     
     
         73 . The method according to  claim 64 , wherein the method comprises high throughput screening technology.  
     
     
         74 . The method according to  claim 65 , wherein the method comprises high throughput screening technology.  
     
     
         75 . The method according to  claim 66 , wherein the method comprises high throughput screening technology.  
     
     
         76 . The method according to  claim 64 , wherein the candidate compounds are small molecules, therapeutics, or drugs.  
     
     
         77 . The method according to  claim 65 , wherein the candidate compounds are small molecules, therapeutics, or drugs.  
     
     
         78 . The method according to  claim 66 , wherein the candidate compounds are small molecules, therapeutics, or drugs.