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Differential cycling rates of Kv4.2 channels in proximal and distal dendrites of hippocampal CA1 pyramidal neurons
Author(s) -
Nestor Michael W.,
Hoffman Dax A.
Publication year - 2012
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20899
Subject(s) - soma , apical dendrite , neuroscience , chemistry , hippocampal formation , biophysics , ampa receptor , dendrite (mathematics) , sk channel , fluorescence recovery after photobleaching , inhibitory postsynaptic potential , ion channel , biology , receptor , nmda receptor , biochemistry , geometry , mathematics , membrane
Abstract The heterogeneous expression of voltage‐gated channels in dendrites suggests that neurons perform local microdomain computations at different regions. It has been shown that A‐type K + channels have a nonuniform distribution along the primary apical dendrite in CA1 pyramidal neurons, increasing with distance from the soma. Kv4.2 channels, which are responsible for the somatodendritic A‐type K + current in CA1 pyramidal neurons, shape local synaptic input, and regulate the back‐propagation of APs into dendrites. Experiments were performed to test the hypothesis that Kv4.2 channels are differentially trafficked at different regions along the apical dendrite during basal activity and upon stimulation in CA1 neurons. Proximal (50–150 μm from the soma, primary and oblique) and distal (>200 μm) apical dendrites were selected. The fluorescence recovery after photobleaching (FRAP) technique was used to measure basal cycling rates of EGFP‐tagged Kv4.2 (Kv4.2g). We found that the cycling rate of Kv4.2 channels was one order of magnitude slower at both primary and oblique dendrites between 50 and 150 μm from the soma. Kv4.2 channel cycling increased significantly at 200 to 250 μm from the soma. Expression of a Kv4.2 mutant lacking a phosphorylation site for protein kinase‐A (Kv4.2gS552A) abolished this distance‐dependent change in channel cycling; demonstrating that phosphorylation by PKA underlies the increased mobility in distal dendrites. Neuronal stimulation by α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA) treatment increased cycling of Kv4.2 channels significantly at distal sites only. This activity‐dependent increase in Kv4.2 cycling at distal dendrites was blocked by expression of Kv4.2gS552A. These results indicate that distance‐dependent Kv4.2 mobility is regulated by activity‐dependent phosphorylation of Kv4.2 by PKA. © 2011 Wiley Periodicals, Inc.