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 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 Cell shortening was measured in voltage-clamped myocytes at 36 degrees C. In solutions where Cs(+) had been replaced by K(+), the voltage dependence of contraction was sigmoidal between -20 and +100 mV in Sham and MI cells.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(+) 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.
Wasserstrom
J A
JA
Institute for Experimental Medical Research, University of Oslo, Ullevaal Hospital, Oslo, Norway. ja-wasserstrom@northwestern.edu
Holt
E
E
Sjaastad
I
I
Lunde
P K
PK
Odegaard
A
A
Sejersted
O M
OM
D000818:Animals; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009532:Nickel / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D016277:Ventricular Function, Left; D014700:Verapamil / Q000494:pharmacology
D019831:Sodium-Calcium Exchanger; D002586:Cesium; D009532:Nickel; D014700:Verapamil; D011188:Potassium