Cardiomyocyte calcium cycling in a naturally occurring German shepherd dog model of inherited ventricular arrhythmia and sudden cardiac deathJournal of Veterinary Cardiology (2013)
AbstractOBJECTIVE: To further characterize arrhythmic mechanisms in German shepherd dogs (GSDs) affected with inherited ventricular arrhythmias by evaluating intracellular calcium cycling and expression of calcium handling genes. ANIMALS: Twenty five GSDs, 9 backcross dogs, and 6 normal mongrel dogs (controls) were studied. The GSDs and backcross dogs were from a research colony of inherited ventricular arrhythmias. The control research dogs were purchased. METHODS:Action potentials (APs) and pseudo-electrocardiograms (ECG) were recorded from left ventricular (LV) wedge preparations of GSDs and normal dogs. Midmyocardial (Mid) LV cells from GSDs and normal mongrels were isolated by enzymatic digestion. Cells were either field stimulated or voltage clamped and calcium transients were measured by confocal microscopy using the indicator Fluo-3AM. Expression of calcium handling genes was measured by quantitative RT-PCR. RESULTS: Mean calcium transient decay (tau) was not different between affected GSDs and control dogs, but striking cell-to-cell variability for tau was observed within affected GSDs and between affected GSDs and controls (P < 0.0001 each); within-dog variability accounted for 75% of total variability. Calcium sparks and afterdepolarizations occurred in GSD but not control cells. ATP2A2/SERCA2a expression was significantly reduced (P = 0.0063) in affected GSDs and inversely correlated (P = 0.0006) with severity of ventricular arrhythmias. CONCLUSIONS: German shepherd dogs with inherited ventricular arrhythmias have electrophysiologic abnormalities in calcium cycling associated with reduced ATP2A2/SERCA2a expression. These animals provide a unique opportunity to study calcium remodeling at the genetic and molecular level in familial ventricular arrhythmias.
Publication DateMarch 14, 2013
Citation InformationSophy A Jesty, S W Jung, J M Cordiero, T M Gunn, et al.. "Cardiomyocyte calcium cycling in a naturally occurring German shepherd dog model of inherited ventricular arrhythmia and sudden cardiac death" Journal of Veterinary Cardiology Vol. 15 Iss. 1 (2013)
Available at: http://works.bepress.com/sophy_jesty/17/