Regional dispersion of L-type calcium current in ventricular myocytes of German shepherd dogs with lethal cardiac arrhythmias.
OBJECTIVE
The purpose of this study was to determine if regional differences in L-type Ca(2+) current (I(Ca,L)) are altered in a German shepherd model of sudden death.


BACKGROUND
German shepherd dogs with inherited sudden cardiac death have reduced sympathetic innervation in the anteroseptal left ventricle that may contribute to arrhythmias in afflicted animals compared to control unafflicted animals. Differences in a number of repolarizing K(+) currents have been identified in this model, but I(Ca,L) has not been studied.


METHODS
We measured action potentials in intact tissue and I(Ca,L) in isolated myocytes from anteroseptal and anterobasal left ventricle.


RESULTS
Action potential plateau level and I(Ca,L) density were significantly lower in unafflicted anteroseptal than in afflicted anteroseptal, afflicted anterobasal, or unafflicted anterobasal. Isoproterenol increased I(Ca,L) density more in the unafflicted anteroseptal group than in the other groups.


CONCLUSIONS
Differences in I(Ca,L) between afflicted and control animals, combined with our earlier finding of regional reductions in I(Kr), provide a likely substrate for the occurrence of pause-dependent arrhythmias in afflicted animals and for the T-wave abnormalities characterizing them.
Protas
Lev
L
Department of Pharmacology, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Sosunov
Eugene A
EA
Anyukhovsky
Evgeny P
EP
Moïse
N Sydney
NS
Rosen
Michael R
MR
Robinson
Richard B
RB
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D015220:Calcium Channels / Q000032:analysis*; D016757:Death, Sudden, Cardiac; D004195:Disease Models, Animal; D004285:Dogs; D032383:Myocytes, Cardiac / Q000502:physiology*; D016276:Ventricular Function
D015220:Calcium Channels