© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Barium block of Kir2 and human cardiac inward rectifier currents: evidence for subunit-heteromeric contribution to native currents
aDepartment of Medicine and Research Center, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec, Canada, H1T 1C8
bDepartment of Medicine, University of Montreal, Montreal, Quebec, Canada
cDepartment of Pharmacology, McGill University, Montreal, Quebec, Canada
dDepartment of Pharmacology, University of Montreal, Montreal, Quebec, Canada
* Corresponding author. Tel.: +1-514-376-3330; fax: +1-514-376-1355. nattel{at}icm.umontreal.ca
Background: Kir2 subunits are believed to underlie the cardiac inwardly rectifying current IK1. The subunit composition of native IK1 currents is uncertain, and it has been suggested that heteromultimer formation may play a role. Methods: We studied Ba2+ block of homo- and heteromeric Kir2 channels in Xenopus oocytes and compared the properties observed to those of human cardiac IK1 in cells isolated from myocardial biopsies of normal human hearts. Results: Homomeric expression of Kir2.1 and Kir2.3 produced currents with similar Ba2+ sensitivities (e.g. IC50 at –120 mV: 16.2±3.4, n = 11 and 18.5±2.1, n = 10, respectively), but these were less sensitive to Ba2+ than native IK1 (4.7±0.5 µM, n = 10, P = 0.001, P<0.001, respectively) and had different Ba2+ blocking kinetics from cardiac IK1. Kir2.2 sensitivity was similar to cardiac IK1 (e.g., 2.8±0.4 µM, Kir2.2, n = 9, vs. 4.7±0.5 µM for IK1), but the blocking kinetics of Kir2.2 were faster than those of IK1. Currents resulting from co-expression of Kir2 subunits had similar Ba2+ sensitivities and blocking kinetics among groups and were similar to IK1 in both Ba2+ sensitivity (e.g., IC50 at –120 mV: 4.5±1.0, 2.5±0.5, and 2.3±0.4 µM for co-injected Kir2.1/2.2, n = 6, Kir2.1/2.3, n = 5, and Kir2.2/2.3, n = 4, respectively) and blocking kinetics. Conclusion: Co-injection of Kir2 subunits results in currents with Ba2+ blocking properties different from homomeric Kir2 expression but similar to cardiac IK1. These observations suggest that a substantial proportion of native IK1 may result from heteromultimer formation among diverse Kir2 family subunits.
KEYWORDS Ion transport; K-channel; Arrhythmia (mechanisms); Ion channels; Sudden death
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