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1 Bioelectricity Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA2 Department of Medicine and Research Center, Montreal Heart Institute and University of Montreal, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada
The rapidly delayed rectifier current (IKr) has been described in ventricular myocytes isolated from many species, as well as from neonatal mice. However, whether IKr is present in the adult mouse heart remains controversial. We used cell-attached patch-clamp recording in symmetrical K+ solutions to assess the presence and behaviour of single IKr channels in adult mouse cardiomyocytes (mIKr). Of 314 patches, 158 (50.1%) demonstrated mIKr currents as compared with 131 (42.3%) for the IK1 channel. Single mIKr channel activity was rarely observed at potentials positive to –10 mV. The slope conductance at negative potentials was 12 pS. Upon repolarization, ensemble-averaged mIKr showed slow deactivation with a biexponential time course. A selective IKr blocker, E-4031 (1 µM), completely blocked mIKr channel activity. Extracellular Ca2+ and Mg2+ at physiological concentrations shifted the activation by 
30 mV, accelerated deactivation kinetics, prolonged long-closed time, and reduced open probability without affecting single-channel conductance, suggesting a direct channel-blocking effect in addition to well-recognized voltage shifts. HERG subunits expressed in Chinese hamster ovary cells produced channels with properties similar to those of mIKr, except for the more-negative activation of the HERG channels. Despite the abundant expression of mIKr, single-channel events were rarely observed during action-potential clamp and 5 µM E-4031 had no detectable effect on the action potential parameters, confirming that mIKr plays at best a minor role in repolarization of adult mouse cardiomyocytes, probably because the modulatory effects of divalent cations prevent significant mIKr opening under physiological conditions.
(Received 10 December 2003;
accepted after revision 6 January 2004;
first published online 23 January 2004)
Corresponding author G. Koren: Bioelectricity Laboratory, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA. Email: gkoren{at}rics.bwh.harvard.edu
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