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Departments of Pediatrics and Cellular and Molecular Physiology Boyer Center for Molecular Medicine Yale University School of Medicine New Haven, CT 06536
Correspondence: Address correspondence to SANG. E-mail steve.goldstein{at}yale.edu; fax 203-737-2290.
The electrocardiogram shown above demonstrates an arrhythmia, called torsades de pointes (sinusoidal trace at right), that is incompatible with the normal pump function of the heart. This particular case was drug-induced and reflects the impairment of specific potassium channels that normally promote the repolarization phase of the cardiac action potential. New insights into the mutations and drugs that compromise the cellular flux of potassium, not only in the heart but also in other organs, are being gained through investigations of the protein components of voltage-gated potassium channels.
Voltage-gated potassium channels provide tightly Controlled, ion-specific pathways across membranes and are key to the normal function of nerves muscles. They arise from the assembly of four pore-forming proteins called 
-subunits. To attain the properties of native currents, -subunits interact with additional molecules such as the mink-related peptides (MiRPs), single-transmembrane subunits encoded by the KCNE genes. Significantly, mutations in KCNE 1, 2 and 3 have been linked either to life-threatening cardiac arrhythmia or a disorder of skeletal muscle, familial periodic paralysis. The capacity of MiRPs to partner with multiple -subunits in experimental cells appears to reflect still undiscovered roles for the KCNE-encoded peptides in vivo. Here, we consider these unique peptides in health disease and discuss future research directions.
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