Human voltage-gated Na <sup>+</sup> and K <sup>+</sup> channel properties underlie sustained fast AP signaling
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
Abstract
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.