Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma

Abstract

To determine whether hepatocyte membrane potential differences (PDs) are depolarized in human HCC and whether depolarization is associated with changes in GABA A receptor expression, hepatocyte PDs and ␥-aminobutyric acid (GABA) A receptor messenger RNA (mRNA) and protein expression were documented in HCC tissues via microelectrode impalement, real-time reverse-transcriptase polymerase chain reaction, and Western blot analysis, respectively. HCC tissues were significantly depolarized (؊19.8 ؎ 1.3 versus ؊25. In recent in vitro studies, we demonstrated that restoration of depolarized malignant hepatocyte cell membrane potential differences (PDs) toward those documented in nonmalignant hepatocytes results in a loss of malignant features, including decreased proliferative activity, absence of colony formation in soft agar, and normalization of phenotypic appearance. 2 Whether HCC tissues are depolarized relative to adjacent nontumor tissues and the mechanisms whereby such depolarization might exist have yet to be reported.

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

“…In previous studies we documented that malignant hepatocyte cell lines and HCC tissues are significantly depolarized (less negative PD values) relative to nonmalignant hepatocytes and non-tumor tissue adjacent to HCC (Erlitzki et al 2000;Minuk et al 2007). We also demonstrated that electrogenic GABA A receptors (which hyperpolarize hepatocytes by increasing chloride influx) are down-regulated in malignant hepatocytes and HCC tissues (Minuk et al 2007). Moreover, restoration of GABAergic activity not only results in hyperpolarization but also inhibits malignant hepatocyte proliferation in vitro and HCC development in vivo (Sun et al 2003).…”

Ex vivo nonviral gene delivery of μ-opioid receptor to attenuate cancer-induced pain

“…Our findings related to zeta potential in oral cancer cells are similar to findings in cancer cells from other tissues including liver, breast, stomach, and pancreas. Cancers in these other tissues have been found to have more positive electric charge compared to normal cells [29; 35; 58]. Surface electric charge of cancer cells seems to be more suitable for transfection compared to normal fibroblasts.…”

Hyperpolarization of the plasma membrane potential provokes reorganization of the actin cytoskeleton and increases the stability of adherens junctions in bovine corneal endothelial cells in culture

“…Thus, PMP changes occur in several physiological situations, such as the transitions between cell cycle stages [Wang et al, 1998;Czarnecki et al, 2000], cell differentiation [Greenwood et al, 1996;Gu et al, 2001;Koegel and Alzheimer, 2001], single-cell migration [Rao et al, 2002], and epithelial wound healing [Chifflet et al, 2005]. Among pathological processes, it has been observed that transformed cells are depolarized in relation to normal cells [Marino et al, 1994;Sun et al, 2003;Minuk et al, 2007]. A main common feature of all these physiological and pathological situations is the occurrence of dramatic modifications in cytoskeletal organization and intercellular adhesion.…”