Bitte benutzen Sie diese Referenz, um auf diese Ressource zu verweisen: doi:10.22028/D291-39557
Volltext verfügbar? / Dokumentlieferung
Titel: Role of sodium channel subtype in action potential generation by neocortical pyramidal neurons
VerfasserIn: Katz, Efrat
Stoler, Ohad
Scheller, Anja
Khrapunsky, Yana
Goebbels, Sandra
Kirchhoff, Frank
Gutnick, Michael J.
Wolf, Fred
Fleidervish, Ilya A.
Sprache: Englisch
Titel: Proceedings of the National Academy of Sciences of the United States of America
Bandnummer: 115
Heft: 30
Seiten: E7184-E7192
Verlag/Plattform: National Academy of Sciences
Erscheinungsjahr: 2018
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Neocortical pyramidal neurons express several distinct subtypes of voltage-gated Na+ channels. In mature cells, Nav1.6 is the dominant channel subtype in the axon initial segment (AIS) as well as in the nodes of Ranvier. Action potentials (APs) are initiated in the AIS, and it has been proposed that the high excitability of this region is related to the unique characteristics of the Nav1.6 channel. Knockout or loss-of-function mutation of the Scn8a gene is generally lethal early in life because of the importance of this subtype in noncortical regions of the nervous system. Using the Cre/loxP system, we selectively deleted Nav1.6 in excitatory neurons of the forebrain and characterized the excitability of Nav1.6-deficient layer 5 pyramidal neurons by patch-clamp and Na+ and Ca2+ imaging recordings. We now report that, in the absence of Nav1.6 expression, the AIS is occupied by Nav1.2 channels. However, APs are generated in the AIS, and differences in AP propagation to soma and dendrites are minimal. Moreover, the channels that are expressed in the AIS still show a clear hyperpolarizing shift in voltage dependence of activation, compared with somatic channels. The only major difference between Nav1.6-null and wild-type neurons was a strong reduction in persistent sodium current. We propose that the molecular environment of the AIS confers properties on whatever Na channel subtype is present and that some other benefit must be conferred by the selective axonal presence of the Nav1.6 channel.
DOI der Erstveröffentlichung: 10.1073/pnas.1720493115
URL der Erstveröffentlichung: https://www.pnas.org/doi/full/10.1073/pnas.1720493115
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-395574
hdl:20.500.11880/35652
http://dx.doi.org/10.22028/D291-39557
ISSN: 1091-6490
0027-8424
Datum des Eintrags: 17-Apr-2023
Bezeichnung des in Beziehung stehenden Objekts: Supporting Information
In Beziehung stehendes Objekt: https://www.pnas.org/doi/suppl/10.1073/pnas.1720493115/suppl_file/pnas.1720493115.sapp.pdf
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Physiologie
Professur: M - Prof. Dr. Frank Kirchhoff
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Dateien zu diesem Datensatz:
Es gibt keine Dateien zu dieser Ressource.


Alle Ressourcen in diesem Repository sind urheberrechtlich geschützt.