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Determination Of The Molecular Mechanisms Of Hyperglycemia-Induced Changes In Cav3.2 Calcium Channel Properties, Ginny Marie Keeling
Determination Of The Molecular Mechanisms Of Hyperglycemia-Induced Changes In Cav3.2 Calcium Channel Properties, Ginny Marie Keeling
Master's Theses
Hyperglycemia can cause altered excitability due to increased CaV3.2 T-type calcium channel function, bestowing diabetics an increased neuropathy risk. The objective of this study was to understand the molecular mechanisms of increased CaV3.2 function during hyperglycemia in vitro, which leads to a 58% increase in current density and increased channel open probability (PO), among other changes. Two major findings are reported in this study:
1) The enzymatic elimination of extracellular N-acetylneuraminic acid (NANA) moieties reversed the increase in current density and the shift in PO, showing that hyper-glycosylation alters channel function in disease.
2) Treatment with GM1 (a ganglioside highly …