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

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.

SUBMITTER: Wilbers R

PROVIDER: S-EPMC10569700 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Wilbers René R Metodieva Verjinia D VD Duverdin Sarah S Heyer Djai B DB Galakhova Anna A AA Mertens Eline J EJ Versluis Tamara D TD Baayen Johannes C JC Idema Sander S Noske David P DP Verburg Niels N Willemse Ronald B RB de Witt Hamer Philip C PC Kole Maarten H P MHP de Kock Christiaan P J CPJ Mansvelder Huibert D HD Goriounova Natalia A NA

Science advances 20231012 41

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 exhi ...[more]

PMID: 37824607

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Project description:Rapid Na+/Ca2+-based action potentials govern essential cellular functions in eukaryotes, from the motile responses of unicellular protists, such as Paramecium [1, 2], to complex animal neuromuscular activity [3]. A key innovation underpinning this fundamental signaling process has been the evolution of four-domain voltage-gated Na+/Ca2+ channels (4D-Cavs/Navs). These channels are widely distributed across eukaryote diversity [4], albeit several eukaryotes, including land plants and fungi, have lost voltage-sensitive 4D-Cav/Navs [5-7]. Because these lineages appear to lack rapid Na+/Ca2+-based action potentials, 4D-Cav/Navs are generally considered necessary for fast Na+/Ca2+-based signaling [7]. However, the cellular mechanisms underpinning the membrane physiology of many eukaryotes remain unexamined. Eukaryotic phytoplankton critically influence our climate as major primary producers. Several taxa, including the globally abundant diatoms, exhibit membrane excitability [8-10]. We previously demonstrated that certain diatom genomes encode 4D-Cav/Navs [4] but also proteins of unknown function, resembling prokaryote single-domain, voltage-gated Na+ channels (BacNavs) [4]. Here, we show that single-domain channels are actually broadly distributed across major eukaryote phytoplankton lineages and represent three novel classes of single-domain channels, which we refer collectively to as EukCats. Functional characterization of diatom EukCatAs indicates that they are voltage-gated Na+- and Ca2+-permeable channels, with rapid kinetics resembling metazoan 4D-Cavs/Navs. In Phaeodactylum tricornutum, which lacks 4D-Cav/Navs, EukCatAs underpin voltage-activated Ca2+ signaling important for membrane excitability, and mutants exhibit impaired motility. EukCatAs therefore provide alternative mechanisms for rapid Na+/Ca2+ signaling in eukaryotes and may functionally replace 4D-Cavs/Navs in pennate diatoms. Marine phytoplankton thus possess unique signaling mechanisms that may be key to environmental sensing in the oceans.

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

Publications

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

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