RT Journal Article
SR Electronic
T1 Nav1.2 and BK channels interaction shapes the action potential in the axon initial segment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.12.488116
DO 10.1101/2022.04.12.488116
A1 Luiza Filipis
A1 Laila Ananda Blömer
A1 Jérôme Montnach
A1 Michel De Waard
A1 Marco Canepari
YR 2022
UL http://biorxiv.org/content/early/2022/04/13/2022.04.12.488116.abstract
AB In neocortical layer-5 pyramidal neurons, the action potential (AP) is generated in the axon initial segment (AIS) when the membrane potential (Vm) reaches the threshold for activation of two diverse voltage-gated Na+ channels, that differ in spatial distribution and biophysical properties. Yet, the understanding of specific functional differences between these two channels remains elusive. Here, using ultrafast Na+, Vm and Ca2+ imaging in combination with partial block of Nav1.2 by a recent peptide, we demonstrate an exclusive role of Nav1.2 in shaping the generating AP. Precisely, Ca2+ influx via Nav1.2 activates BK Ca2+-activated K+ channels determining the amplitude and the early phase of repolarisation of the AP in the AIS. We mimicked this result with a NEURON model where the role of the different ion channels tested reproduced the experimental evidence. The exclusive role of Nav1.2 reported here is important for understanding the physiology and pathology of neuronal excitability.Competing Interest StatementThe authors have declared no competing interest.