Title: A kinetic map of the homomeric voltage-gated potassium channel (Kv) family

Authors: Rajnish Ranjan, Emmanuelle Logette, Michela Marani, Mirjia Herzog, Valérie Tâche, Enrico Scantamburlo, Valérie Buchillier, Henry Markram

Journal: Frontiers in Cellular Neuroscience, 20 August 2019 | https://doi.org/10.3389/fncel.2019.00358

EPFL news: Blue Brain ion channel study beckons first whole-brain simulation

Ion channels (ICs) are proteins that selectively allow ions to diffuse through the cell membrane, creating an electrical potential across the membrane. They are classified in terms of which ion passes through the channel (sodium, potassium, chloride, calcium etc.) and by their gating activity (voltage gating, ligand gating, other forms of gating). Ion channel kinetics are considered among the essential data needed for obtaining a biologically accurate reconstruction of excitable cells.

In landmark papers of 1952, Hodgkin and Huxley developed a mathematical model of ion conductance to demonstrate the role of ion channels in the electrical behavior of excitable nerve cells. Since then, the Hodgkin-Huxley model has been widely used to build ion channel models and to construct biologically realistic neuron models. Currently neuron models use generic ion channel currents representing a class of ion channels to capture electrical behavior of neurons. As the electrical properties of these model neurons faithfully capture those of real neurons, we can trace the causal events of an emergent phenomena down to individual neurons, but we cannot go further down to specific ion channels. However, if the neuron was reconstructed with the specific combination of ion channels expressed in the neuron, properly modeling the kinetics of each ion channel type and their distributions, then it would be valid to trace casual events down to specific ion channels. Obtaining a high quality dataset of the kinetics of the genetically expressed ion channels is therefore the main motivation behind this study.

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There are more than 350 different ion channels expressed in the mammalian brain which includes 145 voltage-gated ion channels of which 40 are voltage-gated potassium (Kv) channels. The genes coding for the Kv channels have been cloned and studied in cell lines for many decades. However, a comprehensive and standardized kinetic characterization of all homomeric Kv channels was missing, especially near physiological temperature.

There are more than 900 Kv ion channel models present in ModelDB. However, the majority of these models are generic Kv channel models which do not represent the kinetics of gene specific ion channel. Moreover, often ion channel kinetics are tweaked to accurately capture neuron electrical behavior resulting in significantly altered ion channel models.

A vast amount of data on Kv channel kinetics is available in the literature. The genes coding for the Kv channels have been cloned and studied in cell lines for many decades. However, a comprehensive biophysical map of the Kv kinetic properties is still missing. The literature focuses on just a few Kv channels, and neglects many others. The lack of consistency limits the value of these data and prevents a consensus on ion channel kinetics. The majority of the previous studies on Kv channels has been conducted at room temperature (RT), which can vary from 18 °C (Heinemann et al., 1996 ) to 28 °C (Hatton et al., 2001). In addition, the raw electrophysiology data needed to build realistic IC models were not publicly available; available data were only in the form of figures or extracted features.

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