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 syndr ome (LQT), To define the function of HERG, we expressed the protein in Xenopus oocytes. The biophysical properties of expressed HERG are nea rly 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 dr ugs that specifically block I-Kr in cardiac myocytes, These data indic ate that HERG proteins form I-Kr channels, but that an additional subu nit may be required for drug sensitivity. Since block of I-Kr is a kno wn mechanism for drug-induced cardiac;arrhythmias, the finding that HE RG encodes I-Kr channels provides a mechanistic link between certain f orms of inherited and acquired LQT.