Date of Completion

12-16-2012

Embargo Period

12-18-2012

Advisors

Anastasios Tzingounis; Wei Sun

Field of Study

Biomedical Engineering

Degree

Master of Science

Open Access

Open Access

Abstract

Small conductance calcium-activated potassium channels (SK) play a fundamental role in synaptic transmission, plasticity, learning and memory (Hammond, 2006; Faber, 2008; Lin et al., 2008) . A very recent study successfully combined single molecule atomic force microscopy (AFM) and toxin pharmacology to quantitatively map SK channels in living neurons (Maciaszek et al., 2012). In addition to localizing native SK channels, this study also showed that SK channel distribution is dynamic with a decrease in SK channel surface expression upon addition of forskolin (FSK), a protein kinase A (PKA) activator. This finding raised further questions about the mechanism through which FSK acts to reduce SK channel expression. In the present work, it was found that FSK acts via the cyclic adenosine-dependent PKA pathway. Also, while PKA activator (FSK) decreased SK channel surface expression, PKA inhibitor (KT 5720) caused the opposite effect. This suggests that there is a tonic PKA activity which suppresses the surface expression of SK channels. Experiments were first carried out in heterologous expression system, HEK293T cells expressing SK channels and then in rat hippocampal neurons expressing native SK channels.

Major Advisor

George Lykotrafitis

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