Published online before print September 18, 2003, doi: 10.1161/01.RES.0000096362.60730.AE
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Submitted on February 28, 2003
Revised on August 27, 2003
Accepted on September 9, 2003
Kv1.5 Is an Important Component of Repolarizing K+ Current in Canine Atrial Myocytes
David Fedida *;
From the Department of Physiology (D.F., J.E., D.F.S.), University of British Columbia, Vancouver, British Columbia, Canada; Cardiome Pharma Corp (D.F., J.C.H.), Vancouver, British Columbia, Canada; and Department of Cardiology (M.L., L.C., D.R.V.W.), Cleveland Clinic Foundation, Cleveland, Ohio.
* To whom correspondence should be addressed. E-mail: fedida{at}interchange.ubc.ca.
Although the canine atrium has proven useful in several experimental models of atrial fibrillation and for studying the effects of rapid atrial pacing on atrial electrical remodeling, it may not fully represent the human condition because of reported differences in functional ionic currents and ion channel subunit expression. In this study, we reassessed the molecular components underlying one current, the ultrarapid delayed rectifier current in canine atrium [IKur(d)], by evaluating the mRNA, protein, immunofluorescence, and currents of the candidate channels. Using reverse transcriptase-polymerase chain reaction, we found that Kv1.5 mRNA was expressed in canine atrium whereas message for Kv3.1 was not detected. Western analysis on cytosolic and membrane fractions of canine tissues, using selective antibodies, showed that Kv3.1 was only detectable in the brain preparations, whereas Kv1.5 was expressed at high levels in both atrial and ventricular membrane fractions. Confocal imaging performed on isolated canine atrial myocytes clearly demonstrated the presence of Kv1.5 immunostaining, whereas that of Kv3.1 was equivocal. Voltage- and current-clamp studies showed that 0.5 mmol/L tetraethylammonium had variable effects on sustained K+ currents, whereas a compound with demonstrated selectivity for hKv1.5 versus Kv3.1, hERG or the sodium channel, fully suppressed canine atrial IKur tail currents and depressed sustained outward K+ current. This agent also increased action potential plateau potentials and action potential duration at 20% and 50% repolarization. These results suggest that in canine atria, as in other species including human, Kv1.5 protein is highly expressed and contributes to IKur.
Key words: potassium channels • hKv1.5 • Kv3.1 • canine heart • atrium
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