Altered action potential of myocardial cells from mouse fetuses with trisomy 16: A model of Down syndrome

Background. Trisomy 21 in humans and trisomy 16 in mice (a model of Down sy ndrome) are associated with increases in rates of depolarization and repola rization and decreases in duration of action potential of neurons, due to o verexpressing protein subunits of Na+ and K+ channels in a gene dose-depend ent manner. These chromosomes also have genes for voltage-gated Na+ and Kchannels expressed by myocardial cells. Thus, it would be expected that hea rt cells would have alterations in their action potentials similar to those found in neurons in both aneuploidies. Methods. Myocardial cells from normal and trisomy 16 mouse fetuses were com pared in relation to their electrical membrane properties using intracellul ar microelectrodes. Results. At 13 and 17 days of gestation, trisomic cells, as compared with c ontrol cells, had higher amplitude and rates of depolarization and repolari zation, with lower duration of plateau of action potential at 25, 50, and 7 5% 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). Conclusions. Myocardial cells of Ts-16 mice showed electrophysiologic alter ations qualitatively similar to those observed in trisomic neurons, in agre ement with the gene dose-dependent hypothesis (see Introduction). (C) 2001 IMSS. Published by Elsevier Science Inc.