Mutations in the KCNE1 gene encoding human minK which cause arrhythmia susceptibility thereby establishing KCNE1 as an LQT gene

A method to screen for drugs which are useful in treating or preventing long QT syndrome, said method comprising:

• a) placing cells transfected with wild-type KVLQT1 and wild-type KCNE1, wherein said cells express wild-type KVLQT1 and wild-type KCNE1, into a bathing solution to measure current;
• b) measuring an induced K+ current in the cells of step (a);
• c) placing cells transfected with wild-type KVLQT1 and mutant KCNE1, wherein said cells express wild-type KVLQT1 and mutant KCNE1, into a bathing solution to measure current;
• d) measuring an induced K+ current in the cells of step (c);
• e) adding a drug to the bathing solution of step (c);
• f) measuring an induced K+ current in the cells of step (g);
• and
• g) determining whether the drug resulted in an induced K+ current more similar to or less similar to the induced K+ current seen in cells expressing wild-type KVLQT1 and wild-type KCNE1 as compared to the current seen in cells expressing wild-type KVLQT1 and mutant KCNE1 in the absence of a drug,
• wherein a drug which results in a current more similar to the current seen in cells expressing wild-type KVLQT1 and wild-type KCNE1 is useful in treating or preventing long QT syndrome.

A method to screen for drugs which are useful in treating or preventing long QT syndrome, said method comprising:

• a) placing cells transfected with wild-type KVLQT1 and wild-type KCNE1, wherein said cells express wild-type KVLQT1 and wild-type KCNE1, into a bathing solution to measure current;
• b) measuring an induced K+ current in the cells of step (a);
• c) placing cells transfected with mutant KVLQT1 and wild-type KCNE1, wherein said cells express mutant KVLQT1 and wild-type KCNE1, into a bathing solution to measure current;
• d) measuring an induced K+ current in the cells of step (c);
• e) adding a drug to the bathing solution of step (c);
• f) measuring an induced K+ current in the cells of step (e);
• and
• g) determining whether the drug resulted in an induced K+ current more similar to or less similar to the induced K+ current seen in cells expressing wild-type KVLQT1 and wild-type KCNE1 as compared to the current seen in cells expressing mutant KVLQT1 and wild-type KCNE1 in the absence of a drug,
• wherein a drug which results in a current more similar to the current seen in cells expressing wild-type KVLQT1 and wild-type KCNE1 is useful in treating or preventing long QT syndrome.

A method for determining the ability of a drug to affect the slow delayed rectifier potassium current (IKs), wherein said method comprises:

• a) placing cells transfected with KVLQT1 and KCNE1, wherein said cells express KVLQT1 and KCNE1, 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 or enhances the IKs by comparing said first induced K+ current with said second induced K+ current.