Martinello et al. 2019

The Brain Simulation Platform "Live Papers"

The subthreshold-active K_v7 current regulates neurotransmission by limiting spike-induced Ca²⁺ influx in hippocampal mossy fiber synaptic terminals

Authors: Katiuscia Martinello¹, Elisabetta Giacalone², Michele Migliore², David A. Brown³, and Mala M. Shah¹

Author information: ¹UCL School of Pharmacy University College London, London WC1N 1AX, UK, ²Institute of Biophysics, National Research Council, 90146 Palermo, Italy, ³Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.

Corresponding author: Author (Mala M. Shah mala.shah@ucl.ac.uk )

Journal: Communications Biology

Download Url: https://www.nature.com/articles/s42003-019-0408-4

Citation: Martinello, K., Giacalone, E., Migliore, M., Brown, D. A., & Shah, M. M. (2019). The subthreshold-active K_v7 current regulates neurotransmission by limiting spike-induced Ca²⁺ influx in hippocampal mossy fiber synaptic terminals. Communications biology, 2(1), 145.

DOI: https://doi.org/10.1038/s42003-019-0408-4

Licence: the Creative Commons Attribution (CC BY) license applies for all files. Under this Open Access license anyone may copy, distribute, or reuse the files as long as the authors and the original source are properly cited.

Abstract:

Little is known about the properties and function of ion channels that affect synaptic terminal-resting properties. One particular subthreshold-active ion channel, the K_v7 potassium channel, is highly localized to axons, but its role in regulating synaptic terminal intrinsic excitability and release is largely unexplored. Using electrophysiological recordings together with computational modeling, we found that the K_v7 current was active at rest in adult hippocampal mossy fiber synaptic terminals and enhanced their membrane conductance. The current also restrained action potential-induced Ca²⁺ influx via N- and P/Q-type Ca²⁺ channels in boutons. This was associated with a substantial reduction in the spike half-width and afterdepolarization following presynaptic spikes. Further, by constraining spike-induced Ca²⁺ influx, the presynaptic K_v7 current decreased neurotransmission onto CA3 pyramidal neurons and short-term synaptic plasticity at the mossy fiber–CA3 synapse. This is a distinctive mechanism by which KV7 channels influence hippocampal neuronal excitability and synaptic plasticity.

Resources

Data and models: data and models used in the paper are available at the links reported below.

Electrophysiological Traces

Download the experimental traces used to reproduce the plots shown in Fig. 3 of the main manuscript at the following link.

ModelDB link and test simulations

A reduced self-consistent set of files needed to reproduce Fig. 4b,c and d of the paper is available on ModelDB

The simulations will reproduce functional effects of Km removal in mossy fiber boutons.
The default settings will reproduce control condition in Fig. 4b,c (Single AP) and Fig. 4d (50Hz Train) of the paper, which refer to the last action potential and all action potentials shown in Fig. 3a and Fig. 3d respectively.

HOWTO: Change settings by turning "on" the "Reset/set parameters" switch to run simulation with your own conductance configuration. Set g_KM=0.0 or both conductances to 0.0 to reproduce respectively red and blue lines of the Fig. 4b,c,d.
Use the "Single AP/50 Hz Train" switch to simulate a single current injection or a 50Hz current pulses train, respectively.
Turn "on" the "Persistent plot" switch to compare plots of different simulations.

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