TY - JOUR
T1 - Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling
AU - Wilbers, René
AU - Metodieva, Verjinia D.
AU - Duverdin, Sarah
AU - Heyer, Djai B.
AU - Galakhova, Anna A.
AU - Mertens, Eline J.
AU - Versluis, Tamara D.
AU - Baayen, Johannes C.
AU - Idema, Sander
AU - Noske, David P.
AU - Verburg, Niels
AU - Willemse, Ronald B.
AU - de Witt Hamer, Philip C.
AU - Kole, Maarten H.P.
AU - de Kock, Christiaan P.J.
AU - Mansvelder, Huibert D.
AU - Goriounova, Natalia A.
PY - 2023/10/13
Y1 - 2023/10/13
N2 - 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.
AB - 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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U2 - 10.1126/sciadv.ade3300
DO - 10.1126/sciadv.ade3300
M3 - Article
C2 - 37824607
AN - SCOPUS:85174751178
SN - 2375-2548
VL - 9
SP - 1
EP - 14
JO - Science advances
JF - Science advances
IS - 41
M1 - eade3300
ER -