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This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/H159    most recent 00375.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, X. Articles by Fliegel, L. Search for Related Content PubMed PubMed Citation Articles by Li, X. Articles by Fliegel, L.

Na⁺/H⁺ exchanger isoform 1 facilitates cardiomyocyte embryonic stem cell differentiation

¹Departments of Biochemistry and Pediatrics, University of Alberta, Edmonton, Alberta, Canada; and ²Institute of Stem Cell Research, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China

Submitted 10 April 2008 ; accepted in final form 5 November 2008

Embryonic stem cells provide one potential source of cardiomyocytes for cardiac transplantation; however, after differentiation of stem cells in vitro, cardiomyocytes usually account for only a minority of cells present. To gain insights into improving cardiomyocyte development from stem cells, we examined the role of the Na⁺/H⁺ exchanger isoform 1 (NHE1) in cardiomyocyte differentiation. NHE1 protein and message levels were induced by treatment of CGR8 cells to form embryoid bodies and cardiomyocytes. The NHE1 protein was present on the cell surface and NHE1 inhibitor-sensitive activity was detected. Inhibition of NHE1 activity during differentiation of CGR8 cells prevented cardiomyocyte differentiation as indicated by decreased message for transcription factors Nkx2-5 and Tbx5 and decreased levels of -myosin heavy chain protein. Increased expression of NHE1 from an adenoviral vector facilitated cardiomyocyte differentiation. Similar results were found with cardiomyocyte differentiation of P19 embryonal carcinoma cells. CGR8 cells were treated to induce differentiation, but when differentiation was inhibited by dispersing the EBs, myocardial development was inhibited. The results demonstrate that NHE1 activity is important in facilitating stem cell differentiation to cardiomyocyte lineage. Elevated NHE1 expression appears to be triggered as part of the process that facilitates cardiomyocyte development.

intracellular pH; adenovirus