Published online before print June 12, 2003, doi: 10.1161/01.RES.0000081596.90205.E2
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Submitted on December 30, 2002
Revised on June 3, 2003
Accepted on June 3, 2003
Effects of Adenovirus-Mediated Sorcin Overexpression on Excitation-Contraction Coupling in Isolated Rabbit Cardiomyocytes
Tim Seidler ;
From the Department of Cardiology and Pneumology (T.S., A.K., A.B., N.T., S.W., H.K., G.H.), Georg-August-University Goettingen, Goettingen, Germany; Institute of Biomedical and Life Sciences (S.L.W.M., S.K., G.L.S.), University of Glasgow, Glasgow, UK; Institute of Comparative Medicine (C.M.L.), University of Glasgow Veterinary School, University of Glasgow, Glasgow, UK; and Department of Medicine (M.B.M.), Cardiology Division, New York University School of Medicine, New York, NY.
* To whom correspondence should be addressed. E-mail: hasenfus{at}med.uni-goettingen.de.
To evaluate the effect of sorcin on cardiac excitation-contraction coupling, adult rabbit ventricular myocytes were transfected with a recombinant adenovirus coding for human sorcin (Ad-sorcin). A 
-galactosidase adenovirus (Ad-LacZ) was used as a control. Fractional shortening in response to 1-Hz field stimulation (at 37°C) was significantly reduced in Ad-sorcin-transfected myocytes compared with control myocytes (2.10±0.05% [n=311] versus 2.42±0.06% [n=312], respectively; P<0.001). Action potential duration (at 20°C) was significantly less in the Ad-sorcin group (458±22 ms, n=11) compared with the control group (520±19 ms, n=10; P<0.05). In voltage-clamped, fura 2-loaded myocytes (20°C), a reduced peak-systolic and end-diastolic [Ca2+]i was observed after Ad-sorcin transfection. L-type Ca2+ current amplitude and time course were unaffected. Caffeine-induced Ca2+ release from the sarcoplasmic reticulum (SR) and the accompanying inward Na+-Ca2+ exchanger (NCX) current revealed a significantly lower SR Ca2+ content and faster Ca2+-extrusion kinetics in Ad-sorcin-transfected cells. Higher NCX activity after Ad-sorcin transfection was confirmed by measuring the NCX current-voltage relationship. -Escin-permeabilized rabbit cardiomyocytes were used to study the effects of sorcin overexpression on Ca2+ sparks imaged with fluo 3 at 145 to 160 nmol/L [Ca2+] using a confocal microscope. Under these conditions, caffeine-mediated SR Ca2+ release was not different between the two groups. Spontaneous spark frequency, duration, width, and amplitude were lower in sorcin-overexpressing myocytes. In summary, sorcin overexpression in rabbit cardiomyocytes decreased Ca2+-transient amplitude predominately by lowering SR Ca2+ content via increased NCX activity. The effect of sorcin overexpression on Ca2+ sparks indicates an effect on the ryanodine receptor that may also influence excitation-contraction coupling.
Key words: excitation-contraction coupling • calcium • cardiac myocytes • adenoviral gene transfer
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