Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling

Wilbers, R.; Metodieva, V. D.; Duverdin, S.; Heyer, D. B.; Galakhova, A. A.; Mertens, E. J.; Versluis, T. D.; Baayen, J. C.; Idema, S.; Noske, D. P.; Verburg, N.; Willemse, R. B.; de Witt Hamer, P. C.; Kole, M. H. P.; de Kock, C. P. J.; Mansvelder, H. D.; Goriounova, N. A.

doi:10.1101/2022.11.29.518317

bioRxiv · 10.1101/2022.11.29.518317

Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling

Wilbers, R.·Metodieva, V. D.·Duverdin, S.·Heyer, D. B.·Galakhova, A. A.·Mertens, E. J.·Versluis, T. D.·Baayen, J. C.·Idema, S.·Noske, D. P.·Verburg, N.·Willemse, R. B.·de Witt Hamer, P. C.·Kole, M. H. P.·de Kock, C. P. J.·Mansvelder, H. D.·Goriounova, N. A.

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Abstract

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have surprisingly fast input-output properties: rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na+) and potassium (K+) currents in human pyramidal neurons can explain their fast input-output properties. Human Na+ and K+ currents exhibited more depolarized voltage-dependence, slower inactivation and faster recovery from inactivation compared with their mouse counterparts. Computational modeling showed that despite lower Na+ channel densities in human neurons, the biophysical properties of Na+ channels resulted in higher channel availability and contributed to fast AP kinetics stability. Finally, human Na+ channel properties also resulted in a larger dynamic range for encoding of subthreshold membrane potential changes. Thus, biophysical adaptations of voltage-gated Na+ and K+ channels enable fast input-output properties of large human pyramidal neurons. One-Sentence SummaryBiophysical properties of Na+ and K+ ion channels enable human neurons to reliably encode fast inputs into output.

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Wilbers, R., Metodieva, V. D., Duverdin, S., Heyer, D. B., Galakhova, A. A., Mertens, E. J., Versluis, T. D., Baayen, J. C., Idema, S., Noske, D. P., Verburg, N., Willemse, R. B., de Witt Hamer, P. C., Kole, M. H. P., de Kock, C. P. J., Mansvelder, H. D., Goriounova, N. A.. 2022-12-02. Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling. https://doi.org/10.1101/2022.11.29.518317

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