Treatment of cardiac disorders by blocking sk4 potassium channel

Abstract

Methods of inducing bradycardia (slowing a heart rate) in a subject in need thereof, treating a medical condition in which inducing bradycardia (slowing a heart rate) is desirable or beneficial in a subject in need thereof and/or treating a medical condition associated with cardiac arrhythmia, are provided. The methods are effected by blocking SK4 channel in SAN cell of the subject and/or by administering to the subject a therapeutically effective amount of a blocker of an SK4 channel. A method of identifying candidate compounds for treating an arrhythmic cardiac disorder, by identifying compounds that reduce a pacing rate of the SAN cells is also provided.

What is claimed is: 
     
         1 . A method of identifying a candidate compound for treating an arrhythmic cardiac disorder in a subject, the method comprising:
 contacting a compound identified as a blocker of SK4 potassium channel with SAN cells; and   determining if the compound reduces a pacing rate of said SAN cells,   wherein a compound that reduces a pacing rate of said SAN cells is identified as a candidate compound for treating an arrhythmic cardiac disorder.   
     
     
         2 . The method of  claim 1 , wherein a compound is identified as a blocker of SK4 potassium channel by:
 contacting the compound with cells expressing SK4 potassium channel; and   determining if a SK4 current amplitude is reduced upon said contacting,   wherein a compound that causes a reduction in said SK4 current amplitude upon said contacting is identified as a blocker of a SK4 channel.   
     
     
         3 . The method of  claim 2 , wherein said cells expressing SK4 potassium channels are transfected cells ectopically expressing said channels. 
     
     
         4 . The method of  claim 1 , wherein contacting the compound with said SAN cells is effected in vitro. 
     
     
         5 . The method of  claim 4 , wherein said SAN cells are obtained from induced pluripotent stem cells-derived pacemaker cells and/or from a subject suffering from an arrhythmic cardiac disorder. 
     
     
         6 . The method of  claim 5 , wherein said subject is a post-natal subject. 
     
     
         7 . The method of  claim 1 , wherein a compound identified as a candidate compound for treating the arrhythmic cardiac disorder is administered to a subject suffering from an arrhythmic cardiac disorder to thereby determine an effect of the compound on a heart rate of the subject. 
     
     
         8 . The method of  claim 7 , wherein said subject is a post-natal subject. 
     
     
         9 . The method of  claim 1 , wherein the arrhythmic cardiac disorder is an atrial arrhythmia. 
     
     
         10 . The method of  claim 1 , wherein the arrhythmic cardiac disorder is a ventricular arrhythmia. 
     
     
         11 . The method of  claim 1 , wherein the arrhythmic cardiac disorder is associated with CPVT. 
     
     
         12 . The method of  claim 1 , wherein said subject is a human subject.