Calendar of Events - Event
Event Scheduled for Aug 23, 2012
Event: Krithika Abiraman: Masters Thesis Defense-Role of Tonic Protein Kinase A on SK2 Channel Expression
Location: UTEB, Room 370
Time: 01:00 pm
Details of Event:
Small conductance calcium-activated potassium channels (SK) play a fundamental role in synaptic transmission, plasticity, learning and memory. A very recent study successfully combined single molecule atomic force microscopy (AFM) and toxin pharmacology to quantitatively map SK channels in living neurons. 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 raised further questions about the mechanism through which FSK acts to reduce SK channel expression. FSK has previously been shown to act via two distinct pathways; cyclic adenosine monophosphate (cAMP) - depedndent PKA pathway and mitogen activated protein kinase (MAPK) pathway. In this study, the role of protein kinase A (PKA) on SK channel cell surface expression was studied by taking advantage of the novel technique of integrating single molecule (AFM) and toxin pharmacology. It was found that FSK indeed acts via the PKA pathway and not the MAPK 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.
Sponsored By: Biomedical Engineering Program
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