The mouse ES cell line hcgp7/#21, which carries a human chromosome 21 (hChr.21), was used as an in vitro model to examine the effects of hChr.21 on cardiomyocyte differentiation. Cardiomyocytes derived from hcgp7/#21 showed a significant delay in the onset of spontaneous beating. The number of Nkx2.5/GFP(+) cardiac progenitor cells was comparable to that in control ES cells and they also expressed comparable mRNA levels for mesodermal markers, cardiac specific transcription factors, contractile proteins, and L-type Ca2+ channels. However, cells from hcgp7/#21 expressed significantly reduced levels of mRNA for Cav3.1 and Cav3.2, which was consistent with the decreased number of cells expressing T-type Ca2+ channels and decreased T-type Ca2+ channel currents. These findings suggest that the presence of human chromosome 21 suppresses expression of T-type Ca2+ channels in cardiomyocytes during differentiation, which may be responsible for delayed onset of spontaneous beating. (c) 2006 Elsevier Inc. All rights reserved.