Protein Kinase Modulation of Dendritic K⁺ Channels in Hippocampus Involves a Mitogen-Activated Protein Kinase Pathway

TLDR

Activation of PKA and PKC enhances backpropagating action potentials in distal CA1 dendrites by downregulating transient K⁺ channels. The study investigates MAPK modulation of dendritic A‑type K⁺ channels in CA1 pyramidal neurons. The authors examined MAPK signaling using phosphospecific antibodies against ppERK and pKv4.2 to assess channel regulation. They found that PKA and PKC converge on ERK‑specific MAPK to reduce dendritic K⁺ current, with ppERK and pKv4.2 localized dendritically and phosphorylation of Kv4.2 subunits mediating dual regulation.

Abstract

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.