Date of Award
5-2016
Document Type
Thesis
Degree Name
Master of Science (MS)
College/School
College of Science and Mathematics
Department/Program
Biology
Thesis Sponsor/Dissertation Chair/Project Chair
Elena Petroff
Committee Member
Vladislav Snitsarev
Committee Member
John Gaynor
Abstract
Glioma are the most common form of brain tumor and carry a particularly poor prognosis that has remained unchanged over the past two decades. Increased activity of large conductance voltage gated and calcium activated potassium channels (BK channels) have been associated with the characteristic invasiveness and proliferation of the disease. Previous work has shown that these channels are inhibited by acid-sensing ion channels (ASIC) at physiological pH (7.4) and that this inhibition is relieved at acidic pH (6.0) commonly found in tumors (Petroff et al. 2008, Petroff et al. 2012). Previous work in our lab has shown that that this regulatory mechanism is in place in primary glial cultures. Due to the role of BK channels in proliferation and migration we hypothesized that this regulatory mechanism may be lost in high grade glioblastoma multiforme. BK channel current was studied electrophysiologically and isolated pharmacologically in U87MG and U118MG glioblastoma multiforme cell lines. Our findings demonstrate that high grade glioma display a heterogeneous outward current profile. BK channels comprise a large part of the current but, unlike primary cultures of glial cells, are no longer regulated by changes in extracellular pH. The activation kinetics of the outward current in glioma is markedly slower than those of BK channel a-subunits alone suggesting that BK channels may be interacting with other proteins or regulatory subunits. Taken together this data suggests that BK channels regulation by ASIC is lost in late stage glioma.
File Format
Recommended Citation
Young, Michael, "Characterization of the Interaction Between ASIC and BK Channels in Glioma Derived Cell Lines" (2016). Theses, Dissertations and Culminating Projects. 670.
https://digitalcommons.montclair.edu/etd/670