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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Electrophysiological properties of human adipose tissue-derived stem cells

¹Department of Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas; and ²Department of Anesthesiology, University of Texas, MD Anderson Cancer Center, Houston, Texas

Submitted 5 March 2007 ; accepted in final form 3 August 2007

Human adipose tissue-derived stem cells (hASCs) represent a potentially valuable cell source for clinical therapeutic applications. The present study was designed to investigate properties of ionic channel currents present in undifferentiated hASCs and their impact on hASCs proliferation. The functional ion channels in hASCs were analyzed by whole-cell patch-clamp recording and their mRNA expression levels detected by RT-PCR. Four types of ion channels were found to be present in hASCs: most of the hASCs (73%) showed a delayed rectifier-like K⁺ current (I_KDR); Ca²⁺-activated K⁺ current (I_KCa) was detected in examined cells; a transient outward K⁺ current (I_to) was recorded in 19% of the cells; a small percentage of cells (8%) displayed a TTX-sensitive transient inward sodium current (I_Na.TTX). RT-PCR results confirmed the presence of ion channels at the mRNA level: Kv1.1, Kv2.1, Kv1.5, Kv7.3, Kv11.1, and hEAG1, possibly encoding I_KDR; MaxiK, KCNN3, and KCNN4 for I_KCa; Kv1.4, Kv4.1, Kv4.2, and Kv4.3 for I_to and hNE-Na for I_Na.TTX. The I_KDR was inhibited by tetraethyl ammonium (TEA) and 4-aminopyridine (4-AP), which significantly reduced the proliferation of hASCs in a dose-dependent manner (P < 0.05), as suggested by bromodeoxyurindine (BrdU) incorporation. Other selective potassium channel blockers, including linopiridine, iberiotoxin, clotrimazole, and apamin also significantly inhibited I_KDR. TTX completely abolished I_Na.TTX. This study demonstrates for the first time that multiple functional ion channel currents such as I_KDR, I_KCa, I_to, and I_Na.TTX are present in undifferentiated hASCs and their potential physiological function in these cells as a basic understanding for future in vitro experiments and in vivo clinical investigations.

proliferation; differentiation; delayed rectifier K⁺ current; voltage-dependent Ca²⁺ current; Ca²⁺-activated K⁺ current; tetrodotoxin-sensitive Na⁺ current; transient outward K⁺ current

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