Enhanced L-type calcium currents in cardiomyocytes from transgenic rats overexpressing SERCA2a.
BACKGROUND
Previous research reported that transgenic rats overexpressing the sarco(endo)plasmic reticulum Ca(2+)-ATPase SERCA2a exhibit improved contractile function of the myocardium. Furthermore, impaired Ca(2+) uptake and reduced relaxation rates in rats with diabetic cardiomyopathy were partially rescued by transgenic expression of SERCA2a in the heart.


OBJECTIVE
To explore whether enhanced Ca(2+) cycling in the cardiomyocytes of SERCA2a transgenic rats is associated with changes in L-type Ca(2+) (I(Ca-L)) currents.


METHODS
The patch-clamp technique was used to measure whole-cell currents in cardiomyocytes from transgenic rats overexpressing SERCA2a and from wild-type (nontransgenic) animals.


RESULTS
The amplitudes of I(Ca-L) currents at depolarizing pulses ranging from -45 mV to 0 mV (350 ms duration, 1 Hz) were significantly higher in cardiomyocytes of SERCA2a transgenic rats than in nontransgenic rats (1985±48 pA [n=32] versus 1612±55 pA [n=28], respectively). The inactivation kinetics of I(Ca-L) showed subtle differences with increased tau fast and tau slow decay constants in cardiomyocytes of SERCA2a transgenic animals. Beta-adrenergic stimulation with 50 nM isoproterenol reduced tau fast and tau slow decay constants in cardiomyocytes of transgenic rats to values that were not significantly different from those in normal cardiomyocytes. Furthermore, isoproterenol enhanced I(Ca-L) currents 3.2-fold and 2.3-fold in cardiomyocytes with and without the SERCA2a transgene, respectively, and this effect was abolished by buffering intracellular Ca(2+) with BAPTA.


CONCLUSIONS
These findings indicate that enhanced Ca(2+) cycling in the hearts of SERCA2a transgenic rats, both under normal conditions and during beta-adrenergic stimulation, involves changes in I(Ca-L) currents. Modified I(Ca-L) kinetics may contribute, to some extent, to the improved contractile function of the myocardium of transgenic rats.
Institut für Vegetative Physiologie;
Andre
A
Kamkin
Irina
I
Kiseleva
Heinz
H
Theres
Jaime-Jürgen
JJ
Eulert-Grehn
Kay-Dietrich
KD
Wagner
Holger
H
Scholz
Roland
R
Vetter
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