Tissue and Species Distribution of mRNA for the i kr -like K + Channel, ERG

Abstract

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 encode the fast component of the delayed rectifier K + current (I Kr ) found in heart. To date, the published electrophysiological and pharmacological 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 different 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 were 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 uniformly throughout the heart. The erg transcript is expressed at relatively high levels, being ≈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 and are abundant in the brain, retina, thymus, and adrenal gland and are also found in skeletal muscle, lung, and cornea. Since there were no published reports of an I Kr -like current in the rat heart, electrophysiological studies were performed to test whether the significant level 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-4031–sensitive current was observed, which is consistent with the presence of I Kr . These results strengthen the link between erg and the native I Kr in heart and suggest that erg may play an important role in other noncardiac tissues.