Characterization of hERG1a and hERG1b potassium channels-a possible role for hERG1b in the I (Kr) current.
I (Kr) is the fast component of the delayed rectifier potassium currents responsible for the repolarization of the cardiac muscle. The molecular correlate underlying the I (Kr) current has been identified as the hERG1 channel. Recently, two splice variants of the hERG1 alpha-subunit, hERG1a and hERG1b, have been shown to be co-expressed in human cardiomyocytes. In this paper, we present the electrophysiological characterization of hERG1a, hERG1b, and co-expressed hERG1a/b channels in a mammalian expression system using the whole-cell patch clamp technique. We also quantified the messenger RNA (mRNA) levels of hERG1a and hERG1b in human cardiac tissue, and based on the expressed ratios, we evaluated the resulting currents in Xenopus laevis oocytes. Compared to hERG1a channels, activation was faster for both hERG1b and hERG1a/b channels. The deactivation kinetics was greatly accelerated in the presence of hERG1b, whereas no difference in the time constant of inactivation was observed. The voltage-dependent recovery from inactivation was also similar. However, the time constant of recovery from inactivation was significantly faster for hERG1b channels compared to hERG1a and hERG1a/b. Quantification of hERG1a and hERG1b mRNA in the human heart showed that hERG1b mRNA constitutes, on average, 19% in the right atrium and 12% in the left ventricle of the total hERG1 mRNA. Expression of the observed ratios of hERG1a to hERG1b in X. laevis oocytes showed that these ratios are indeed sufficient to change the deactivation phenotype markedly. The present work suggests that hERG1b is likely to play a role in the formation of the native I (Kr) current.
Larsen
Anders Peter
AP
The Danish National Research Foundation Center for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.
Olesen
Søren-Peter
SP
Grunnet
Morten
M
Jespersen
Thomas
T
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014982:Xenopus laevis
D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D004247:DNA