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

Excitation-contraction (E-C) coupling was investigated in rat hearts 6 wk a fter induction of myocardial infarction (MI) by ligation of the left corona ry artery. Heart weight was increased by 74% and left ventricular end-diast olic pressure was 23 +/- 2 mmHg in MI compared with 8 +/- 2 mmHg in sham-op erated 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 Cell shortening was measured in voltage- clamped myocytes at 36 degrees C. In solutions where Cs+ had been replaced by K+, the voltage dependence of contraction was sigmoidal between -20 and +100 mV in Sham and MI cells.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 mu M) blocked L-type Ca2+ curre nt and reduced contraction in Sham cells by similar to 50% (P < 0.01) but d id not decrease contraction significantly in MI cells at test potentials ab ove +10 mV. Verapamil-insensitive contractions were blocked by Ni2+ (5 mM). Na+/Ca2+ exchange current was doubled in MI compared with Sham cells at te st potentials between -20 and +80 mV (P < 0.05), whereas mRNA and protein e xpression increased by 30-40%. Finally, voltage dependence of contraction w as bell shaped in Na+-free solutions, but contraction was significantly inc reased in MI cells over a wider voltage range (P < 0.05). The insensitivity to Ca2+ channel block in MI cells may result from an increased contributio n of the Na+/Ca2+ exchanger to triggering of E-C coupling. These results su ggest significant changes in E-C coupling in the hypertrophy and failure th at develop in response to extensive MI.