ABSTRACT
The transient voltage-gated K+ current (IA) mediated by Kv4.2 in CA1 hippocampal pyramidal neurons regulates dendritic excitability, synaptic plasticity, and learning. Here we report that Ca2+ entry mediated by the voltage-gated Ca2+ channel subunit Cav2.3 regulates Kv4.2 function in CA1 pyramidal neurons through Ca2+ binding auxiliary subunits known as K+ channel interacting proteins (KChIPs). We characterized an interaction between Cav2.3 and Kv4.2 using immunofluorescence colocalization, coimmunoprecipitation, electron microscopy, FRAP, and FRET. We found that Ca2+-entry via Cav2.3 increases Kv4.2-mediated whole-cell current due in part to an increase in Kv4.2 surface expression. In hippocampal neurons, pharmacological block of Cav2.3 reduced whole-cell IA. We also found reduced IA in Cav2.3 knockout mouse neurons with a loss of the dendritic IA gradient. Furthermore, the Cav2.3-Kv4.2 complex was found to regulate the size of synaptic currents and spine Ca2+ transients. These results reveal an intermolecular Cav2.3-Kv4.2 complex impacting synaptic integration in CA1 hippocampal neurons.
Competing Interest Statement
The authors have declared no competing interest.