Bone marrow mesenchymal stem cells upregulate transient outward potassium currents in postnatal rat ventricular myocytes

Abstract

Bone marrow mesenchymal stem cell (BMSC) transplantation has been shown to effectively improve cardiac function in experimental animals and patients with myocardial infarction and heart hypertrophy. BMSCs exert potent effects on cardiomyocytes through the inhibition of cardiac apoptosis, the attenuation of cardiac inflammation, etc. However, novel biological actions of BMSCs on cardiomyocytes remain to be explored. The present study was designed to investigate whether BMSCs affect electrophysiological features of neonatal rat ventricular myocytes (NRVMs). BMSCs and NRVMs were indirectly co-cultured at a ratio of 1:10 with a semi-permeable membrane. We found that compared with mono-cultured NRVMs, co-cultured NRVMs exhibited an obvious increase of transient outward potassium current (I(to)), accompanied by significant changes in activation, inactivation and recovery of I(to). Meanwhile, K(V)4.2 mRNA which encodes the channel carrying I(to) was more abundant in co-cultured NRVMs than mono-cultured NRVMs. The increases in basic fibroblast growth factor (bFGF) and insulin growth factor-1 (IGF-1) levels were observed in culture medium of BMSCs. bFGF but not IGF-1 upregulated the K(V)4.2 mRNA expression and enhanced I(to) currents. Taken together, we conclude that BMSCs upregulate I(to) of NRVMs, at least partially, by secreting bFGF that in turn upregulates K(V)4.2 expression and alters the kinetics of I(to).