Date of Award

2012

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Neuroscience

Abstract

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 decreased during hyperglycemia and diabetes) also reversed the changes in current density due to hyperglycemia.

Our results suggest that the CaV3.2 glycosylation status is likely altered during hyperglycemia, affecting channel function; in addition, GM1 is a specific inhibitor of CaV3.2 and its depletion may contribute to current dis-inhibition in disease.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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