Referenced in: none

Automatically associated channels: Kir1.1 , Kv1.2 , Kv1.4 , Kv2.1 , Nav1.2 , SK4

Title: GATA-4 induces changes in electrophysiological properties of rat mesenchymal stem cells.

Authors: Hong-xia Li, Ya-Feng Zhou, Bin Jiang, Xin Zhao, Ting-bo Jiang, Xun Li, Xiang-jun Yang, Wen-ping Jiang

Journal, date & volume: Biochim. Biophys. Acta, 2014 Jun , 1840, 2060-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24582939

Abstract
Transplanted mesenchymal stem cells (MSC) can differentiate into cardiac cells that have the potential to contribute to heart repair following ischemic injury. Overexpression of GATA-4 can significantly increase differentiation of MSC into cardiomyocytes (CM). However, the specific impact of GATA-4 overexpression on the electrophysiological properties of MSC-derived CM has not been well documented.Adult rat bone marrow MSC were retrovirally transduced with GATA-4 (MSC(GATA-4)) and GFP (MSC(Null)) and subsequently co-cultured with neonatal rat ventricular cardiomyocytes (CM). Electrophysiological properties and mRNA levels of ion channels were assessed in MSC using patch-clamp technology and real-time PCR.MSC(GATA-4) exhibited higher levels of the TTX-sensitive Na(+) current (INa.TTX), L-type calcium current (ICa.L), transient outward K(+) current (Ito), delayed rectifier K(+) current (IKDR) and inwardly rectifying K(+) current (IK1) channel activities reflective of electrophysiological characteristics of CM. Real-time PCR analyses showed that MSC(GATA-4) exhibited upregulated mRNA levels of Kv1.2, Kv2.1, SCN2a1, CCHL2a, KV1.4 and Kir1.1 channels versus MSC(Null). Interestingly, MSC(GATA-4) treated with IGF-1 neutralizing antibodies resulted in a significant decrease in Kir1.1, Kv2.1, KV1.4, CCHL2a and SCN2a1 channel mRNA expression. Similarly, MSC(GATA-4) treated with VEGF neutralizing antibodies also resulted in an attenuated expression of Kv2.1, Kv1.2, Kv1.4, Kir1.1, CCHL2a and SCN2a1 channel mRNAs.GATA-4 overexpression increases Ito, IKDR, IK1, INa.TTX and ICa.L currents in MSC. Cytokine (VGEF and IGF-1) release from GATA-4 overexpressing MSC can partially account for the upregulated ion channel mRNA expression.Our results highlight the ability of GATA4 to boost the cardiac electrophysiological potential of MSC.