INCORPORATION OF THE TROPONIN REGULATORY COMPLEX OF POSTISCHEMIC STUNNED PORCINE MYOCARDIUM REDUCES MYOFILAMENT CALCIUM SENSITIVITY IN RABBIT PSOAS SKELETAL-MUSCLE FIBERS
Ks. Mcdonald et al., INCORPORATION OF THE TROPONIN REGULATORY COMPLEX OF POSTISCHEMIC STUNNED PORCINE MYOCARDIUM REDUCES MYOFILAMENT CALCIUM SENSITIVITY IN RABBIT PSOAS SKELETAL-MUSCLE FIBERS, Journal of Molecular and Cellular Cardiology, 30(2), 1998, pp. 285-296
Decreased calcium sensitivity of tension in post-ischemic myocardium i
s thought to be a mechanism of depressed function in stunning. The pur
pose of this study was to determine if the decrease in calcium sensiti
vity of tension results from ischemia and/or reperfusion-induced alter
ations in the thin filament regulatory troponin, The experiments utili
zed an open-chest porcine model of regional LAD myocardial stunning th
at has previously been shown to cause a decrease in calcium sensitivit
y of tension in permeabilized myocytes, Stunning was induced by 45 min
of low-now ischemia to the left anterior descending (LAD) coronary ar
tery perfusion bed, which was followed by 30 min of reperfusion. Regio
nal LAD function after reperfusion was 0.5 +/- 2.8%, as assessed by sy
stolic wall thickening (v 23.9 +/- 4.1% thickening in control, P < 0.0
01). Core biopsy samples from control circumflex and stunned LAD myoca
rdium were acquired from each heart (n = 9) after LAD reperfusion, and
were used to obtain purified troponin complexes. Isometric tension-pC
a relationships were measured in permeabilized psoas skeletal fibers b
efore and after partial exchange of cardiac troponin from either contr
ol circumflex (n = 6) or stunned LAD (n = 8) myocardium for endogenous
skeletal troponin. Calcium sensitivity of tension as assessed by pCa(
50) (i.e. pCa for half-maximal tension) was unchanged after exchange o
f troponin from control circumflex myocardium (pCa(50) = 5.98 +/- 0.02
v 5.96 +/- 0.06), but there was a significant decrease in calcium sen
sitivity of tension after exchange of troponin from stunned LAD myocar
dium (pCa(50) = 5.97 +/- 0.07 v 5.82 +/- 0.05, P < 0.05). We conclude
that the decrease in calcium sensitivity of tension in postischemic st
unned myocardium is, in part, due to ischemia and/or reperfusion-induc
ed alterations in the cardiac troponin regulatory complex. (C) 1998 Ac
ademic Press Limited.