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Kinetic and thermodynamic modeling of a voltage-gated sodium channel

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Abstract

Like all biological and chemical reactions, ion channel kinetics are highly sensitive to changes in temperature. Therefore, it is prudent to investigate channel dynamics at physiological temperatures. However, most ion channel investigations are performed at room temperature due to practical considerations, such as recording stability and technical limitations. This problem is especially severe for the fast voltage-gated sodium channel, whose activation kinetics are faster than the time constant of the standard patch-clamp amplifier at physiological temperatures. Thus, biologically detailed simulations of the action potential generation evenly scale the kinetic models of voltage-gated channels acquired at room temperature. To quantitatively study voltage-gated sodium channels' temperature sensitivity, we recorded sodium currents from nucleated patches extracted from the rat's layer five neocortical pyramidal neurons at several temperatures from 13.5 to 30 °C. We use these recordings to model the kinetics of the voltage-gated sodium channel as a function of temperature. We show that the temperature dependence of activation differs from that of inactivation. Furthermore, the data indicate that the sustained current has a different temperature dependence than the fast current. Our kinetic and thermodynamic analysis of the current provided a numerical model spanning the entire temperature range. This model reproduced vital features of channel activation and inactivation. Furthermore, the model also reproduced action potential dependence on temperature. Thus, we provide an essential building block for the generation of biologically detailed models of cortical neurons.

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Data availability

Data will be available upon a request to corresponding author. Model code is available from ModelDB (note to reviewers: model code will be deposited on acceptance of article).

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Acknowledgements

This work was supported by grants from the Israel Science Foundation to AK (#225/20).

Funding

This work was supported by grants from the Israel Science Foundation to AK (#225/20).

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Authors and Affiliations

  1. The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar Ilan University, 52900, Ramat Gan, Israel

    Alon Korngreen

  2. The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, 52900, Ramat Gan, Israel

    Mara Almog, Nurit Degani-Katzav & Alon Korngreen

Authors
  1. Mara Almog
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  2. Nurit Degani-Katzav
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  3. Alon Korngreen
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Contributions

AK and MA designed the study, performed the experiments, and analyzed the data. NDK and AK drafted and revised the manuscript. All authors read and approved the final version of the manuscript for publication.

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Correspondence to Alon Korngreen.

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Almog, M., Degani-Katzav, N. & Korngreen, A. Kinetic and thermodynamic modeling of a voltage-gated sodium channel. Eur Biophys J 51, 241–256 (2022). https://doi.org/10.1007/s00249-022-01591-3

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  • DOI: https://doi.org/10.1007/s00249-022-01591-3

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