TISSUE AND SPECIES DISTRIBUTION OF MESSENGER-RNA FOR THE I-KR-LIKE K+CHANNEL, ERG

The human K+ channel gene, HERG, has been linked to the type 2 form of the autosomal dominant long-QT syndrome and has been suggested to enc ode the fast component of the delayed rectifier K+ current (I-Kr) foun d in heart. To date, the published electrophysiological and pharmacolo gical data on the Xenopus-expressed HERG are very similar but are not identical to those of the endogenous I-Kr. In an effort to provide a d ifferent type of correlative data on the relationship between erg and I-Kr, cDNA fragments of erg homologues from guinea pig, rabbit, human, dog, and rat wen cloned and used to test for the presence of erg mRNA in cardiac tissue. RNase protection assays reveal that erg message is found in the hearts of all five species and that it is expressed unif ormly throughout the heart. The erg transcript is expressed at relativ ely high levels, being approximate to 50% more abundant than the most prevalent Kv-class K+ channel transcript in canine ventricle (Kv4.3). erg transcripts were found to have a wide tissue distribution in rat a nd are abundant in the brain, retina, thymus, and adrenal gland and ar e also found in skeletal muscle, lung, and cornea. Since there were no published reports of an I-Kr-like current in the rat heart, electroph ysiological studies were performed to test whether the significant lev er of erg message in rat heart was correlated with the presence of an I-Kr-like current in rat. In isolated rat ventricular myocytes, an E-4 031-sensitive current was observed, which is consistent with the prese nce of I-Kr. These results strengthen the link between erg and the nat ive I-Kr in heart and suggest that erg may play an important role in o ther noncardiac tissues.