MinK-related genes, formation of potassium channels and association with cardiac arrhythmia

Abstract

The present invention is directed to genes and gene products related to Min-K which form ion channels and to a process for diagnosis of ion channel disorders, including long QT syndrome (LQT). For example, KCNE2 forms I Kr potassium channels and is associated with LQT. LQT is diagnosed in accordance with the present invention by analyzing the DNA sequence of KCNE2 of an individual to be tested and comparing the respective DNA sequence to the known DNA sequence of a normal KCNE2 gene. Alternatively, these MinK-related genes of an individual to be tested can be screened for mutations which cause ion channel disorders, including LQT. Prediction of ion channel disorders, including LQT, will enable practitioners to prevent the disorders using existing medical therapy. This invention is further directed to the discovery that the HERG and KCNE2 (also known as MiRP1) proteins coassemble to form a cardiac I Kr potassium channel.

1 - 52 . (canceled)  
     
     
         53 . A method for determining the ability of a drug to affect the fast delayed rectifier potassium current (I Kr ), wherein said method comprises: 
 a) placing cells expressing wild-type HERG and wild-type KCNE2 into a bathing solution to measure current;    b) measuring or detecting a first induced K +  current in the cells of step (a);    c) adding a drug to the bathing solution of step (a);    d) measuring a second induced K +  current in the cells of step (c); and    e) determining whether addition of said drug in step (c) inhibits, enhances, or alters the I Kr  by comparing said first induced K +  current with said second induced K +  current.      54 - 68  (canceled).