A MECHANISTIC LINK BETWEEN AN INHERITED AND AN ACQUIRED CARDIAC-ARRHYTHMIA - HERG ENCODES THE I-KR POTASSIUM CHANNEL

Mutations in HERG cause an inherited cardiac arrhythmia, long QT syndrome (LQT), To define the function of HERG, we expressed the protein in Xenopus oocytes. The biophysical properties of expressed HERG are nearly identical to the rapidly activating delayed rectifier K+ current (I-Kr) in cardiac myocytes. HERG current is K+ selective, declines with depolarizations above 0 mV, is activated by extracellular K+, and is blocked by lanthanum. Interestingly, HERG current is not blocked by drugs that specifically block I-Kr in cardiac myocytes, These data indicate that HERG proteins form I-Kr channels, but that an additional subunit may be required for drug sensitivity. Since block of I-Kr is a known mechanism for drug-induced cardiac;arrhythmias, the finding that HERG encodes I-Kr channels provides a mechanistic link between certain forms of inherited and acquired LQT.