Myocardial infarction in rat eliminates regional heterogeneity of AP profiles, I(to) K(+) currents, and [Ca(2+)](i) transients.
Transient outward K(+) current density (I(to)) 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), I(to), and intracellular Ca(2+) concentration ([Ca(2+)](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, I(to) 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, I(to) 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 I(to) 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 [Ca(2+)](i) transients amplitude was higher in the SEP compared with the RVW in sham myocytes. These regional differences in APD and [Ca(2+)](i) transients were eliminated by MI. Our results demonstrate that the significant regional differences in I(to) density, APD, and [Ca(2+)](i) between RVW and SEP are linked to a variation in Kv4.2 expression, which largely disappears after MI.
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129-0060, USA.
Roger
R
Kaprielian
Rajan
R
Sah
Tin
T
Nguyen
Alan D
AD
Wickenden
Peter H
PH
Backx
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D006346:Heart Septum / Q000502:physiology; D051665:Kv1.4 Potassium Channel; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D011917:Rats, Inbred Lew; D051672:Shal Potassium Channels; D016276:Ventricular Function
C496979:Kcna4 protein, rat; C497020:Kcnd2 protein, rat; C497023:Kcnd3 protein, rat; D051665:Kv1.4 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D011188:Potassium; D002118:Calcium