Normal contractions triggered by I(Ca,L) in ventricular myocytes from rats with postinfarction CHF.
Attenuated L-type Ca(2+) current (I(Ca,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 I(Ca,L) (4.5 +/- 0.3 vs. 3.8 +/- 0.3 pApF(-1) at 23 degrees C and 9.4 +/- 0.5 vs. 8.4 +/- 0.5 pApF(-1) at 37 degrees C), the bell-shaped voltage-contraction relationship in Cs(+) solutions (fractional shortening, 15.2 +/- 1.0% vs. 14.3 +/- 0.7%, respectively, at 23 degrees C and 7.5 +/- 0.4% vs. 6.7 +/- 0.5% at 37 degrees C) and the sigmoidal voltage-contraction relationship in K(+) solutions. Caffeine-induced Ca(2+) release and sarcoplasmic reticulum Ca(2+)-ATPase-to-phospholamban ratio were not different. Thus CHF contractions triggered by I(Ca,L) were normal, and the contractile deficit was only seen in undialyzed cardiomyocytes stimulated from -70 mV.
Institute for Experimental Medical Research, University of Oslo, 0407 Oslo, Norway. ivar.sjaastad@ioks.uio.no
Ivar
I
Sjaastad
Janny
J
Bøkenes
Fredrik
F
Swift
J Andrew
JA
Wasserstrom
Ole M
OM
Sejersted
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013696:Temperature; D000099211:Phospholamban
D002110:Caffeine; D002118:Calcium; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D010726:Phosphodiesterase Inhibitors; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban