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1 Heart and Stroke Richard Lewar Centre and Departments of Physiology and Medicine, University of Toronto; 2 Division of Cardiology, University Health Network, Toronto, Ontario, Canada M5G 2C4; and 3 Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129-0060
Transient outward K+ current density (Ito) has been shown to vary between different regions of the normal myocardium and to be reduced in heart disease. In this study, we measured regional changes in action potential duration (APD), Ito, and intracellular Ca2+ concentration ([Ca2+]i) transients of ventricular myocytes derived from the right ventricular free wall (RVW) and interventricular septum (SEP) 8 wk after myocardial infarction (MI). At +40 mV, Ito density in sham-operated hearts was significantly higher (P < 0.01) in the RVW (15.0 ± 0.8 pA/pF, n = 47) compared with the SEP (7.0 ± 1.1 pA/pF, n = 18). After MI, Ito density was not reduced in SEP myocytes but was reduced (P < 0.01) in RVW myocytes (8.7 ± 1.0 pA/pF, n = 26) to levels indistinguishable from post-MI SEP myocytes. These changes in Ito density correlated with Kv4.2 (but not Kv4.3) protein expression. By contrast, Kv1.4 expression was significantly higher in the RVW compared with the SEP and increased significantly after MI in RVW. APD measured at 50% or 90% repolarization was prolonged, whereas peak [Ca2+]i transients amplitude was higher in the SEP compared with the RVW in sham myocytes. These regional differences in APD and [Ca2+]i transients were eliminated by MI. Our results demonstrate that the significant regional differences in Ito density, APD, and [Ca2+]i between RVW and SEP are linked to a variation in Kv4.2 expression, which largely disappears after MI.
right ventricle; septum; heart disease; contraction
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