Abstract
Excitation-contraction (E-C) coupling was investigated in rat hearts
6 wk after induction of myocardial infarction (MI) by ligation
of the left coronary artery. Heart weight was increased by 74\% and
left ventricular end-diastolic pressure was 23 +/- 2 mmHg in MI
compared with 8 +/- 2 mmHg in sham-operated controls (Sham, P < 0.001).
Cell shortening was measured in voltage-clamped myocytes at 36 degrees
C. In solutions where Cs$^+$ had been replaced by K$^+$, the
voltage dependence of contraction was sigmoidal between -20 and +100
mV in Sham and MI cells. Verapamil (20 microM) blocked L-type Ca$^2+$
current and reduced contraction in Sham cells by approximately 50\%
(P < 0.01) but did not decrease contraction significantly in MI
cells at test potentials above +10 mV. Verapamil-insensitive contractions
were blocked by Ni$^2+$ (5 mM). Na$^+$/Ca$^2+$ exchange
current was doubled in MI compared with Sham cells at test potentials
between -20 and +80 mV (P < 0.05), whereas mRNA and protein expression
increased by 30-40\%. Finally, voltage dependence of contraction
was bell shaped in Na$^+$-free solutions, but contraction was
significantly increased in MI cells over a wider voltage range
(P < 0.05). The insensitivity to Ca$^2+$ channel block in MI
cells may result from an increased contribution of the Na$^+$/Ca$^2+$
exchanger to triggering of E-C coupling. These results suggest significant
changes in E-C coupling in the hypertrophy and failure that develop
in response to extensive MI.
- 10924080
- animals,
- cells,
- cesium,
- congestive,
- contraction,
- cultured,
- exchanger,
- failure,
- function,
- gov't,
- heart
- heart,
- infarction,
- left,
- male,
- membrane
- myocardial
- myocardium,
- nickel,
- non-u.s.
- p.h.s.,
- potassium,
- potentials,
- rats,
- research
- sodium-calcium
- support,
- u.s.
- ventricles,
- ventricular
- verapamil,
- wistar,
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