Functional Coupling of Cav2.3 and BK Potassium Channels Regulates Action Potential Repolarization and Short-Term Plasticity in the Mouse Hippocampus.

Jakob J Gutzmann,Dax A Hoffman,Lin Lin

doi:10.3389/fncel.2019.00027

Abstract

Voltage-gated ion channels are essential for signal generation and propagation in neurons and other excitable cells. The high-voltage activated calcium-channel Cav2.3 is expressed throughout the central and peripheral nervous system, and within CA1 hippocampal pyramidal neurons it is localized throughout the somato-dendritic region and dendritic spines. Cav2.3 has been shown to provide calcium for other calcium-dependent potassium channels including small-conductance calcium-activated potassium channels (SK), but big-conductance calcium-activated potassium channels (BK) have been thought to be activated by calcium from all known voltage-gated calcium channels, except Cav2.3. Here we show for the first time that CA1 pyramidal cells which lack Cav2.3 show altered action potential (AP) waveforms, which can be traced back to reduced SK- and BK-channel function. This change in AP waveform leads to strengthened synaptic transmission between CA1 and the subiculum, resulting in increased short-term plasticity. Our results demonstrate that Cav2.3 impacts cellular excitability through functional interaction with BK channels, impacting communication between hippocampal subregions.

Highlights

Voltage-gated ion channels are responsible for the active electrical properties of excitable cells like muscles and neurons
We found no significant difference in the excitatory postsynaptic potentials (EPSPs) amplitude or decay-time between WT and Cav2.3 KO (Figures 6F,G), we found that the facilitation index, i.e., the ratio between the second evoked EPSP and the first evoked EPSP, is significantly larger for Cav2.3 KO animals than their WT littermates, indicating increased synaptic efficacy between CA1 and subiculum in Cav2.3 KO
We show that a genetic deletion of Cav2.3 leads to altered action potential (AP) waveform in CA1 pyramidal cells, and that this alteration leads to increased synaptic efficacy at the CA1-subiculum synapse

Summary

Introduction

Voltage-gated ion channels are responsible for the active electrical properties of excitable cells like muscles and neurons. The high-voltage activated calcium-channel Cav2.3 is expressed on the soma, as well as on dendrites and spines of hippocampal pyramidal cells (Magee and Johnston, 1995; Parajuli et al, 2012) and mediates the majority of their R-type calcium current (Sochivko et al, 2002). Sochivko et al (2002) found no compensatory expression of other calcium channels after the loss of Cav2.3 in CA1 or neocortical pyramidal neurons, or in granule cells of the dentate gyrus. Cav2.3 has been described as a regulator of cellular excitability, either directly (Park et al, 2010) or indirectly through small-conductance calcium-activated potassium channels (SK; Zaman et al, 2011)

Methods

Results

Conclusion