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The Journal of Neuroscience, July 23, 2008, 28(30):7513-7519; doi:10.1523/JNEUROSCI.1951-08.2008

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Brief Communications
Protein Kinase A Mediates Activity-Dependent Kv4.2 Channel Trafficking

Rebecca S. Hammond, Lin Lin, Michael S. Sidorov, Andrew M. Wikenheiser, and Dax A. Hoffman

Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-3715

Correspondence should be addressed to Dax A. Hoffman, Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, 35 Lincoln Drive, MSC 3715, Building 35, Room 3C-905, Bethesda, MD 20892-3715. Email: hoffmand{at}mail.nih.gov

The A-type potassium channel subunit Kv4.2 influences hippocampal function through regulation of dendritic excitability, and changes in Kv4.2 surface expression alter synaptic plasticity. Recent data from our laboratory demonstrate that EGFP (enhanced green fluorescent protein)-tagged Kv4.2 channels located in dendritic spines are internalized in an activity-dependent manner after synaptic stimulation and during chemically induced long-term potentiation. However, the molecular trigger for Kv4.2 internalization remains unknown. Here we examined the role of protein kinase A (PKA) in Kv4.2 activity-dependent trafficking. In hippocampal neurons, PKA activation with forskolin or 8-Br-cAMP induced Kv4.2 internalization from dendritic spines, whereas PKA inhibition with H89 prevented AMPA-induced internalization. Furthermore, introduction of a point mutation at the C-terminal PKA phosphorylation site of Kv4.2 (S552A) prevented the AMPA-induced internalization of Kv4.2. Together, these data demonstrate that Kv4.2 activity-dependent internalization requires PKA phosphorylation of Kv4.2 at serine 522.

Key words: potassium channel; IA; Kv4.2; trafficking; hippocampus; excitability; PKA


Received Dec. 13, 2007; accepted June 9, 2008.

Correspondence should be addressed to Dax A. Hoffman, Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, 35 Lincoln Drive, MSC 3715, Building 35, Room 3C-905, Bethesda, MD 20892-3715. Email: hoffmand{at}mail.nih.gov






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