Molecular Properties of Neuronal Dendritic K+ Channels
In this proposal we will are testing the specific hypothesis that Kv4 alpha subunits assemble with KChIP proteins and DPP proteins to form the A current that is found CA1 pyramidal neurons. We will test if the levels of A current are dynamically regulated by changes in subunit gene expression or posttranslational modifications.
Specific Aim 1: Test the prediction that Kv4 alpha subunits and KChIP auxiliary subunits are required for formation of the dendritic A current in CA1 pyramidal neurons.
Specific Aim 2: Analysis of the A current functional expression set point in hippocampal pyramidal neurons. The goal of Specific Aim 2 is to determine whether KChIPs or Kv4 subunits are limiting A current expression in different subcellular compartments by measuring the sensitivity of the basal A current to the expression of a particular subunit gene.
Specific Aim 3: Analysis of the role of other auxililary subunits in shaping the expression and functional properties of native A currents and heterologous Kv4 channels.
Specific Aim 4: Test the hypothesis that CamKII phosporylation of Kv4.2 subunits and Ca2+ dependent induction of A current by KChIPs are required to redistribute A current throughout the dendritic tree in order to normalize the Ca2+ influx in response to backpropagating action potentials.
Relevance of the project to IDDRC mission:
DPP proteins have been identified as potential genes involved in Autism and ALS. The goal of our study is to determine the cellular roles of the DPP proteins as a possible modulatory of dendritic KV channel function. By determining the role of DPP protein in neurons we hope to gain additional insight into the potential links between abnormal DPP protein function and the appearance of Autism and ALS.