Enhanced Ca(2+) release and Na/Ca exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis.
BACKGROUND
Ventricular arrhythmias are a major cause of sudden death in patients with heart failure and hypertrophy. The dog with chronic complete atrioventricular block (CAVB) has biventricular hypertrophy and ventricular arrhythmias and is a useful model to study underlying cellular mechanisms. We investigated whether changes in Ca(2+) homeostasis are part of the contractile adaptation to CAVB and might contribute to arrhythmogenesis.


RESULTS
In enzymatically isolated myocytes, cell shortening, Ca(2+) release from the sarcoplasmic reticulum (SR), and SR Ca(2+) content were enhanced at low stimulation frequencies. Ca(2+) influx through L-type Ca(2+) channels was unchanged, but Ca(2+) influx via the Na/Ca exchanger was increased and contributed to Ca(2+) loading of the SR. Inward Na/Ca exchange currents were also larger. Changes in Ca(2+) fluxes were less pronounced in the right versus left ventricle.


CONCLUSIONS
Enhanced Na/Ca exchange activity may improve contractile adaptation to CAVB but at the same time facilitate arrhythmias by (1) increasing the propensity to Ca(2+) overload, (2) providing more inward current leading to (nonhomogeneous) action potential prolongation, and (3) enhancing (arrhythmogenic) currents during spontaneous Ca(2+) release.
Sipido
K R
KR
Laboratory of Experimental Cardiology, University of Leuven, Belgium. karin.sipido@med.kuleuven.ac.be
Volders
P G
PG
de Groot
S H
SH
Verdonck
F
F
Van de Werf
F
F
Wellens
H J
HJ
Vos
M A
MA
D000220:Adaptation, Biological; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D006327:Heart Block / Q000503:physiopathology*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D008564:Membrane Potentials; D009200:Myocardial Contraction / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D015854:Up-Regulation
D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D002118:Calcium