Altered Action Potential of Myocardial Cells from Mouse Fetuses with Trisomy 16: A Model of Down Syndrome

Background y 21 in humans and trisomy 16 in mice (a model of Down syndrome) are associated with increases in rates of depolarization and repolarization and decreases in duration of action potential of neurons, due to overexpressing protein subunits of Na+ and K+ channels in a gene dose-dependent manner. These chromosomes also have genes for voltage-gated Na+ and K+ channels expressed by myocardial cells. Thus, it would be expected that heart cells would have alterations in their action potentials similar to those found in neurons in both aneuploidies. s dial cells from normal and trisomy 16 mouse fetuses were compared in relation to their electrical membrane properties using intracellular microelectrodes. s and 17 days of gestation, trisomic cells, as compared with control cells, had higher amplitude and rates of depolarization and repolarization, with lower duration of plateau of action potential at 25, 50, and 75% of repolarization. This suggests that Ca2+ influx is reduced in trisomic cells, which could impair Ca2+-dependent fetal myocardial functions (i.e., contractility or matrix secretion). sions dial cells of Ts-16 mice showed electrophysiologic alterations qualitatively similar to those observed in trisomic neurons, in agreement with the gene dose-dependent hypothesis (see Introduction).