Mostrar el registro sencillo del ítem
dc.contributor.author
Vivekananda, Umesh
dc.contributor.author
Novak, Pavel
dc.contributor.author
Bello, Oscar Daniel
dc.contributor.author
Korchev, Yuri E.
dc.contributor.author
Krishnakumar, Shyam S.
dc.contributor.author
Volynski, Kirill E.
dc.contributor.author
Kullmann, Dimitri M.
dc.date.available
2022-12-29T17:10:34Z
dc.date.issued
2017-02
dc.identifier.citation
Vivekananda, Umesh; Novak, Pavel; Bello, Oscar Daniel; Korchev, Yuri E.; Krishnakumar, Shyam S.; et al.; Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 114; 9; 2-2017; 2395-2400
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/182836
dc.description.abstract
Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog-digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CHANNELOPATHY
dc.subject
POTASSIUM CHANNEL
dc.subject
SYNAPTIC TRANSMISSION
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.subject.classification
Biofísica
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.subject.classification
Neurociencias
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-12-27T18:07:45Z
dc.identifier.eissn
1091-6490
dc.journal.volume
114
dc.journal.number
9
dc.journal.pagination
2395-2400
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Vivekananda, Umesh. University College London; Estados Unidos
dc.description.fil
Fil: Novak, Pavel. Queen Mary University Of London; Reino Unido
dc.description.fil
Fil: Bello, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. University College London; Estados Unidos
dc.description.fil
Fil: Korchev, Yuri E.. Imperial College London; Reino Unido
dc.description.fil
Fil: Krishnakumar, Shyam S.. University College London; Estados Unidos. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Volynski, Kirill E.. University College London; Estados Unidos
dc.description.fil
Fil: Kullmann, Dimitri M.. University College London; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/lookup/doi/10.1073/pnas.1608763114
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1608763114
Archivos asociados