Tissue and species distribution of mRNA for the IKr-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 encode the fast component of the delayed rectifier K+ current (IKr) 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 IKr. In an effort to provide a different type of correlative data on the relationship between erg and IKr. 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 approximately 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 IKr-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 IKr-like current in rat. In isolated rat ventricular myocytes, an E-4031-sensitive current was observed, which is consistent with the presence of IKr. These results strengthen the link between erg and the native IKr in heart and suggest that erg may play an important role in other noncardiac tissues.
Wymore
R S
RS
Department of Physiology and Biophysics, State University of New York at Stony Brook 11794, USA. rwymore@brain.bio.sunysb.edu
Gintant
G A
GA
Wymore
R T
RT
Dixon
J E
JE
McKinnon
D
D
Cohen
I S
IS
D000595:Amino Acid Sequence; D000818:Animals; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins; D004285:Dogs; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006168:Guinea Pigs; D006801:Humans; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000032:analysis*; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D027682:Cation Transport Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG