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Articles in PresS, published online ahead of print May 2, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00518.2001
Submitted on June 13, 2001
Accepted on April 15, 2002
1 Massachusetts General Hospital, Cardiovascular Research Center CNY, Charlestown, MA, USA
2 Heart & Stroke Richard Lewar Centre and the Depts. of Physiology and Medicine, University of Toronto, Toronto,, Ontario, Canada
3 Heart & Stroke Richard Lewar Centre and the Depts. of Physiology and Medicine, University of Toronto, Toronto,, Ontario, Canada; Division of Cardiology, University Health Network, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: p.backx{at}utoronto.ca.
Transient outward potassium (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 [Ca2+]i transients of ventricular myocytes derived from the right ventricular wall (RVW) and interventricular septum (SEP) following 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 to the SEP (7.0±1.1 pA/pF n=18). Following 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 to the SEP and increased significantly following MI in RVW. Action potential duration (APD), measured at 50% or 90% repolarization was prolonged while peak [Ca2+]i transients amplitude was higher in the SEP compared to 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 following MI.
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