TY - JOUR
T1 - Altered E-C coupling in rat ventricular myocytes from failing hearts 6 wk after MI
AU - Wasserstrom, J. Andrew
AU - Holt, Even
AU - Sjaastad, Ivar
AU - Kristian Lunde, P. E.R.
AU - Ødegaard, Annlaug
AU - Sejersted, Ole M.
PY - 2000
Y1 - 2000
N2 - 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 Cell shortening was measured in voltage-clamped myocytes at 36°C. In solutions where Cs+ had been replaced by K+, the voltage dependence of contraction was sigmoidal between -20 and +100 mV in Sham and MI cells.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 μM) blocked L-type Ca2+ current and reduced contraction in Sham cells by ~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 Ni2+ (5 mM). Na+/Ca2+ 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 Ca2+ 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.
AB - 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 Cell shortening was measured in voltage-clamped myocytes at 36°C. In solutions where Cs+ had been replaced by K+, the voltage dependence of contraction was sigmoidal between -20 and +100 mV in Sham and MI cells.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 μM) blocked L-type Ca2+ current and reduced contraction in Sham cells by ~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 Ni2+ (5 mM). Na+/Ca2+ 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 Ca2+ 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.
KW - Calcium channels
KW - Contractility
KW - Excitation-contraction coupling
KW - Heart failure
KW - Hypertrophy
KW - Myocardial infarction
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U2 - 10.1152/ajpheart.2000.279.2.h798
DO - 10.1152/ajpheart.2000.279.2.h798
M3 - Article
C2 - 10924080
AN - SCOPUS:0033851234
SN - 0363-6135
VL - 279
SP - H798-H807
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2 48-2
ER -