Date of Award
Master of Science (MS)
College of Science and Mathematics
Thesis Sponsor/Dissertation Chair/Project Chair
Glioma, the most common and aggressive type of brain cancer, involves faster glial proliferation. Increased activity of large conductance calcium and voltage-activated potassium (BK) channels has been shown to accelerate glial proliferation. Our previous studies have shown that Acid Sensing Ion Channels (ASICs) inhibit BK current at physiological pH levels, and that this inhibition can be relieved at acidic pH (Petroff et al, 2008). ASICs can therefore act as endogenous pH-dependent regulators of BK channel activity. Both normal glia and glioma tissue express BK and ASIC channels. We hypothesized that ASICs may function as endogenous inhibitors of glial cell growth through their inhibition of BK channels, and that at a site of trauma or injury, a disruption of this interaction by an acidic pH environment may lead to increased glial proliferation. If this is the case, then the growth of ASIC la knockout glia would be pH-independent in the range of pH 7.0 - 7.4, and the presence of a BK channel blocker, charybdotoxin (CTx), should decrease cell growth at all pH levels in wild type and knockout glia. Our data demonstrate that, in both neonatal and wild type glial cells, the proliferation in culture was increased at pH 7.0 as compared to normal pH conditions (7.4), and that CTx inhibited glial growth at both pH levels. Adult mouse ASIC la knockout glia exhibited similar proliferation rates at pH 7.4 and 7.0, and CTx inhibited proliferation to the same level as in wild type cells. Thus, in the absence of ASIC la, the pH-dependent regulation of glial growth is lost in ASIC la knockout glia. This work is supported by the NIH NS070260 grant to EP.
Guercio, Jennifer C., "Molecular Mechanisms Involved in Regulation of Glial Cell Proliferation" (2012). Theses, Dissertations and Culminating Projects. 864.