R-type voltage-gated Ca2+ channels mediate A-type K+ current regulation of synaptic input in hippocampal dendrites

Abstract

The transient K+ current (IA) carried by pore forming Kv4.2 subunits regulates the propagation of synaptic input, dendritic excitability, and synaptic plasticity in CA1 pyramidal neuron dendrites of the hippocampus. We report that the Ca2+ channel subunit Cav2.3 regulates IA in this cell type. We first identified Cav2.3 as a Kv4.2 interacting protein in a proteomic screen and we confirmed Cav2.3-Kv4.2 complex association using multiple techniques. Functionally, Cav2.3 Ca2+-entry increases Kv4.2-mediated whole-cell current due to an increase in Kv4.2 surface expression. Using pharmacology and Cav2.3 knockout mice, Cav2.3 was found to promote whole-cell IA and the increasing gradient of IA in the apical dendrite distal to the neuronal soma. Furthermore, the loss of Cav2.3 function leads to enhancement of synaptic currents and spine Ca2+ influx. These results present Cav2.3 and Kv4.2 as integral constituents of an ion channel complex that impacts synaptic function in the hippocampus.