Effect of ASIC‐BK Interaction on Migration of PC12 Cells

Abstract

Acid sensing ion channels (ASICs) and large conductance calcium and voltage‐activated potassium (BK) channels are expressed in normal glia as well as glioma tumors. At reduced pH, ASIC channels are activated and the inhibition of BK is relieved (Petroff et al., 2008). Lactic acidosis has been associated with cerebral trauma and tumors (Andersen et al. 1988 and Wike‐Hooley 1984). Our previous studies suggest that pH‐dependent relief of BK inhibition by ASICs increases cell proliferation in glial cells. We hypothesized that the activation of BK channels by a decrease in pH and may also promote cell migration. PC12, a rat pheochromocytoma cell line that expresses both ASIC and BK channels, was used as a model system. The cells were cultured at physiological pH 7.4 and reduced pH (7.0), in the presence and in the absence of 200nM of charybdotoxin, a BK channel blocker, and assessed for cell migration. Our data show that activation of BK channels by reduced pH or inhibition of BK channels by charybdotoxin have no effect on PC12 cell migration. These results indicate that in PC12 cells, the molecular mechanism involved in cellular proliferation by activation of BK channels might be independent from the mechanisms involved in cell migration. This work is supported by the R15 NIH grant to E.P.