Referenced in: none

Automatically associated channels: Kv1.1 , Kv1.4 , Kv1.5 , Kv2.1 , Kv3.1 , Kv4.3 , Slo1

Title: 5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells.

Authors: Bartosz Balana, Cecilia Nicoletti, Ihor Zahanich, Eva M Graf, Torsten Christ, Sabine Boxberger, Ursula Ravens

Journal, date & volume: Cell Res., 2006 Dec , 16, 949-60

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17160070

Abstract
Previously, mouse bone marrow-derived stem cells (MSC) treated with the unspecific DNA methyltransferase inhibitor 5-azacytidine were reported to differentiate into cardiomyocytes. The aim of the present study was to investigate the efficiency of a similar differentiation strategy in human mononuclear cells obtained from healthy bone marrow donors. After 1-3 passages, cultures were exposed for 24 h to 5-azacytidine (3 mciroM) followed by 6 weeks of further culture. Drug treatment did not induce expression of myogenic marker MyoD or cardiac markers Nkx2.5 and GATA-4 and did not yield beating cells during follow-up. In patch clamp experiments, approximately 10-15% of treated and untreated cells exhibited L-type Ca(2+) currents. Almost all cells showed outwardly rectifying K(+) currents of rapid or slow activation kinetics. Mean current amplitude at +60 mV doubled after 6 weeks of treatment compared with time-matched controls. Membrane capacitance of treated cells was significantly larger than in controls 2 weeks after treatment and remained high after 6 weeks. Expression levels of mRNAs for the K(+) channels Kv1.1, Kv1.5, Kv2.1, Kv4.3 and KCNMA1 and for the Ca(2+) channel Ca(v)1.2 were not affected by 5-azacytidine. Treatment with potassium channel blockers tetraethylammonium and clofilium at concentrations shown previously to inhibit rapid or slowly activating K(+) currents of hMSC inhibited proliferation of these cells. Our results suggest that despite the absence of differentiation of hMSC into cardiomyocytes, treatment with 5-azacytidine caused profound changes in current density.