Dax Hoffman's Unit on Molecular Neurophysiology and Biophysics continues to investigate the role of the voltage-gated potassium channel subunits in the regulation of dendritic excitability and synaptic integration of hippocampal neurons. Over the past year, the Unit discovered that distance-dependent dendritic Kv4.2 mobility is regulated by activity-dependent phosphorylation of Kv4.2 by protein kinase A (PKA). The source of PKA modulation was identified as a novel accessory subunit for Kv4.2A, AKAP79/150, which provides a platform for dynamic PKA regulation of Kv4.2 expression, critically affecting neuronal excitability. Studies in heterologous expression systems showed that Kv4 a-subunits interact with an additional auxiliary subunit, DPP6, which was recently identified in large copy-number variant screens as an Autism Spectrum Disorder and ALS target gene. In dendritic recordings from DPP6 knockout mice, the laboratory discovered that DPP6 is critical for generating the A-type potassium current gradient observed in CA1 dendrites. Loss of this gradient led to hyper-excitable dendrites, with implications for information storage and coding.
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