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1 Institute for Experimental Medical Research, University of Oslo; 2 Department of Cardiology, Heart and Lung Center, Ullevaal University Hospital, 0407 Oslo, Norway; and 3 Cardiology Division, Department of Medicine, and the Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, Illinois 60611
Attenuated L-type
Ca2+ current (ICa,L), or
current-contraction gain have been proposed to explain impaired cardiac
contractility in congestive heart failure (CHF). Six weeks after
coronary artery ligation, which induced CHF, left ventricular myocytes
from isoflurane-anesthetized rats were current or voltage clamped from
70 mV. In both cases, contraction and contractility were
attenuated in CHF cells compared with cells from sham-operated rats
when cells were only minimally dialyzed using high-resistance
microelectrodes. With patch pipettes, cell dialysis caused attenuation
of contractions in sham cells, but not CHF cells. Stepping from
50
mV, the following variables were not different between sham and CHF,
respectively: peak ICa,L (4.5 ± 0.3 vs.
3.8 ± 0.3 pApF
1 at 23°C and 9.4 ± 0.5 vs.
8.4 ± 0.5 pApF
1 at 37°C), the bell-shaped
voltage-contraction relationship in Cs+ solutions
(fractional shortening, 15.2 ± 1.0% vs. 14.3 ± 0.7%, respectively, at 23°C and 7.5 ± 0.4% vs. 6.7 ± 0.5% at
37°C) and the sigmoidal voltage-contraction relationship in
K+ solutions. Caffeine-induced Ca2+ release and
sarcoplasmic reticulum Ca2+-ATPase-to-phospholamban ratio
were not different. Thus CHF contractions triggered by
ICa,L were normal, and the contractile deficit
was only seen in undialyzed cardiomyocytes stimulated from
70 mV.
electrophysiology; myocardial infarction; sarcoplasmic reticulum Ca2+ ATPase; phospholamban; caffeine; L-type Ca2+ current; congestive heart failure
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