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The Journal of Neuroscience, June 15, 2002, 22(12):4860-4868
Protein Kinase Modulation of Dendritic K+ Channels in Hippocampus Involves a Mitogen-Activated Protein Kinase Pathway
Li-Lian Yuan, J. Paige Adams, Michael Swank, J. David Sweatt, and Daniel Johnston Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
We investigated mitogen-activated protein kinase (MAPK) modulation of dendritic, A-type K+ channels in CA1 pyramidal neurons in the hippocampus. Activation of cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) leads to an increase in the amplitude of backpropagating action potentials in distal dendrites through downregulation of transient K+ channels in CA1 pyramidal neurons in the hippocampus. We show here that both of these signaling pathways converge on extracellular-regulated kinases (ERK)-specific MAPK in mediating this reduction in dendritic K+ current, which is confirmed, in parallel, by biochemical assays using phosphospecific antibodies against the ppERK and pKv4.2. Furthermore, immunostaining indicates dendritic localization of ppERK and pKv4.2. Taken together, these results demonstrate that dendritic, A-type K+ channels are dually regulated by PKA and PKC through a common downstream pathway involving MAPK, and the modulation of these K+ channels may be accounted for by the phosphorylation of Kv4.2 subunits.
Key words: dendrite; A-type K+ channel; MAPK; PKA; PKC; hippocampus
Copyright © 2002 Society for Neuroscience 0270-6474/02/22124860-09$05.00/0
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