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

SUMMARY The transient K + current (I A ) 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 Ca 2+ channel subunit Cav2.3 regulates I A 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 Ca 2+ -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 I A and the increasing gradient of I A in the apical dendrite distal to the neuronal soma. Furthermore, the loss of Cav2.3 function leads to enhancement of synaptic currents and spine Ca 2+ influx. These results present Cav2.3 and Kv4.2 as integral constituents of an ion channel complex that impacts synaptic function in the hippocampus.