Membrane potential differences and GABAA receptor expression in hepatic tumor and non-tumor stem cells

The ability to differentiate tumor initiating stem cells (TISCs) from healthy, normal stem cells (NSCs) could have important diagnostic and therapeutic implications for patients with hepatocellular carcinoma (HCC). The aim of this study was to document and compare cell membrane potentials (PDs) and GABA(A) receptor subunit expression in hepatic TISCs and NSCs. PD values were determined in CD133(+) Huh-7 TISCs and CD133(+) WBF344 NSCs by single channel microelectrode impalement. GABA(A) receptor subunit expression was documented using immunohistochemistry (IH) in both cell lines as well as surgically resected HCC and healthy liver tissues. TISCs were significantly depolarized compared with NSCs (-4.0 +/- 1.8 versus -11.0 +/- 2.4 mV, respectively; p < 0.05). GABA(A) alpha(6) subunit expression was either absent or markedly attenuated, while gamma(3) subunit expression was abundant in TISCs and HCC compared with NSCs and healthy liver tissues. Exposure to the GABA(A) receptor agonist muscimol caused hyperpolarization of TISCs (Delta -4.4 +/- 1.1) but depolarization of NSCs (Delta + 5.2 +/- 2.3) and attenuation of TISC proliferative activity. We conclude that TISCs and NSCs have significantly different cell membrane potentials and these differences are associated with differences in GABA(A) receptor subunit expression.