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

Research group Kole
Publication year 2023
Published in Science advances
Authors René Wilbers, Verjinia D Metodieva, Sarah Duverdin, Djai B Heyer, Anna A Galakhova, Eline J Mertens, Tamara D Versluis, Johannes C Baayen, Sander Idema, David P Noske, Niels Verburg, Ronald B Willemse, Philip C de Witt Hamer, Maarten H P Kole, Christiaan P J de Kock, Huibert D Mansvelder, Natalia A Goriounova

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have unexpectedly 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. Last, 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.

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