© 1998 American Heart Association, Inc.
Editorial |
Calcium Pump Overexpression and Myocardial Function
Implications for Gene Therapy of Myocardial Failure
Correspondence to Gerd Hasenfuss, MD, Universität Göttingen, Zentrum Innere Medizin, Abteilung Kardiologie und Pneumologie, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. E-mail hasenfus@med.uni-goettingen.de
Key Words: Ca2+-ATPase overexpression • myocardium • gene therapy • heart failure
The contraction-relaxation cycle of the heart is
controlled by the sequential rise and fall of the cytosolic calcium
concentration. Calcium entry through L-type calcium channels during the
action potential serves to trigger calcium release from the
sarcoplasmic reticulum (SR) leading to activation of contractile
proteins and force generation (for review, see Reference 11 ). In
addition, there is calcium influx by reverse-mode sodium-calcium
exchange. The contribution of calcium influx through L-type calcium
channels, or sodium calcium exchange, and of SR calcium release to
systolic calcium transients differs from species to
species.2 The global increase in calcium is
immediately followed by calcium removal, resulting in subsequent
deactivation of the contractile machinery and myocardial relaxation.
Calcium removal from the cytosol occurs by the activity of the SR pump,
by exchange of calcium for sodium via the sarcolemmal sodium-calcium
exchanger (Na+-Ca2+
exchanger), by mitochondrial calcium uptake, and by calcium extrusion
via the sarcolemmal calcium pump.1 Again, the
contribution of these systems removing calcium from the cytosol to the
decay of the calcium transient and to subsequent relaxation varies in a
species-dependent manner. Using the rapid-cooling contracture
technique, Bers et al suggested that in rat ventricular
myocardium, 
92% of calcium removal occurs by SR calcium
uptake and only 7% by
Na+-Ca2+
exchange.3 4 In other species (human, rabbit,
ferret, cat, and guinea pig) the balance is more in the range of 70%
to 75% SR calcium uptake and 25% to 30%
Na+-Ca2+
exchange.3 4 According to these studies, calcium
uptake by mitochondria and
This article has been cited by other articles:
 |
|
 |
|
  L. S. Maier, C. Wahl-Schott, W. Horn, S. Weichert, C. Pagel, S. Wagner, N. Dybkova, O. J. Muller, M. Nabauer, W.-M. Franz, et al. Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats Cardiovasc Res, September 1, 2005; 67(4): 636 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lohn, M. Furstenau, V. Sagach, M. Elger, W. Schulze, F. C. Luft, H. Haller, and M. Gollasch Ignition of Calcium Sparks in Arterial and Cardiac Muscle Through Caveolae Circ. Res., November 24, 2000; 87(11): 1034 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Lehnart, P. M. L. Janssen, W. M. Franz, J. K. Donahue, J. H. Lawrence, E. Marban, J. Prestle, and G. Hasenfuss Preservation of myocardial function after adenoviral gene transfer in isolated myocardium Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H986 - H991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hajjar, F. del Monte, T. Matsui, and A. Rosenzweig Prospects for Gene Therapy for Heart Failure Circ. Res., March 31, 2000; 86(6): 616 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Miyamoto, F. del Monte, U. Schmidt, T. S. DiSalvo, Z. B. Kang, T. Matsui, J. L. Guerrero, J. K. Gwathmey, A. Rosenzweig, and R. J. Hajjar Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure PNAS, January 18, 2000; 97(2): 793 - 798. [Abstract] [Full Text] [PDF]
|
|