© 1997 American Heart Association, Inc.
Articles |
Electrophysiological Characterization of an Alternatively Processed ERG K+ Channel in Mouse and Human Hearts
From the Department of Medicine, University of Calgary (Canada).
Correspondence to H.J. Duff, MD, FRCPC, Department of Medicine, University of Calgary, 3330 Hospital Dr, NW, Calgary, Alberta, Canada, T2N 4N1.
Abstract Mutants of HERG, the human form of ERG (the
ether-a-go-go–related K+ channel gene), are
responsible for some forms of the long-QT syndrome, an abnormality of
cardiac repolarization. HERG was cloned from brain and has properties
similar but not identical to the rapidly activating component of the
native cardiac K+ channel current
(IKr). We identified in the mouse an
alternatively processed form of ERG (MERG B) that is expressed
abundantly in heart but only in trace amounts in brain. MERG B has a
unique 36–amino acid NH2-terminal domain that is strongly
basic and considerably shorter than the 376–amino acid
NH2-terminal domain of HERG. When expressed in
Xenopus oocytes, the kinetics of activation and deactivation
of the MERG B current were best fit by a biexponential function, with
the fast components dominant over the slow components. The fast
component of activation had a mean 
value of 163±16 ms at -20 mV
and 8±4 ms at +20 mV (n=4). The fast component of deactivation had a
mean value of 145±29 ms at -20 mV and 12±4 ms at -90 mV (n=4).
The MERG B current was blocked by the selective
IKr blocker, dofetilide, with an
IC50 of 54 nmol/L. In addition, we isolated HERG B, the
human homologue of MERG B, which has
electrophysiological characteristics
qualitatively similar to those of MERG B. We have identified ERG B, an
alternatively processed isoform of the ERG gene, expressed selectively
in heart and with electrophysiological
characteristics similar to those of native cardiac
IKr.
Key Words: K+ channel • ether-a-go-go–related gene • long-QT syndrome • mouse • alternative processing
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