Article,

Altered E-C coupling in rat ventricular myocytes from failing hearts 6 wk after MI.

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Am. J. Physiol. Heart Circ. Physiol., 279 (2): H798-807 (August 2000)

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 Cell shortening was measured in voltage-clamped myocytes at 36 degrees C. In solutions where Cs$^+$ had been replaced by K$^+$, the voltage dependence of contraction was sigmoidal between -20 and +100 mV in Sham and MI cells.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.

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