Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

Autores
Vivekananda, Umesh; Novak, Pavel; Bello, Oscar Daniel; Korchev, Yuri E.; Krishnakumar, Shyam S.; Volynski, Kirill E.; Kullmann, Dimitri M.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Vivekananda, Umesh. University College London; Estados Unidos
Fil: Novak, Pavel. Queen Mary University Of London; Reino Unido
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
Fil: Korchev, Yuri E.. Imperial College London; Reino Unido
Fil: Krishnakumar, Shyam S.. University College London; Estados Unidos. University of Yale. School of Medicine; Estados Unidos
Fil: Volynski, Kirill E.. University College London; Estados Unidos
Fil: Kullmann, Dimitri M.. University College London; Estados Unidos
Materia
CHANNELOPATHY
POTASSIUM CHANNEL
SYNAPTIC TRANSMISSION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182836
Acceder
id CONICETDig_9c281617df66e24c69beb30672eb691b
oai_identifier_str oai:ri.conicet.gov.ar:11336/182836
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarizationVivekananda, UmeshNovak, PavelBello, Oscar DanielKorchev, Yuri E.Krishnakumar, Shyam S.Volynski, Kirill E.Kullmann, Dimitri M.CHANNELOPATHYPOTASSIUM CHANNELSYNAPTIC TRANSMISSIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Although 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.Fil: Vivekananda, Umesh. University College London; Estados UnidosFil: Novak, Pavel. Queen Mary University Of London; Reino UnidoFil: 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 UnidosFil: Korchev, Yuri E.. Imperial College London; Reino UnidoFil: Krishnakumar, Shyam S.. University College London; Estados Unidos. University of Yale. School of Medicine; Estados UnidosFil: Volynski, Kirill E.. University College London; Estados UnidosFil: Kullmann, Dimitri M.. University College London; Estados UnidosNational Academy of Sciences2017-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182836Vivekananda, 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; 2395-24000027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/lookup/doi/10.1073/pnas.1608763114info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1608763114info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:28:01Zoai:ri.conicet.gov.ar:11336/182836instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:28:01.742CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
title Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
spellingShingle Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
Vivekananda, Umesh
CHANNELOPATHY
POTASSIUM CHANNEL
SYNAPTIC TRANSMISSION
title_short Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
title_full Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
title_fullStr Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
title_full_unstemmed Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
title_sort Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
dc.creator.none.fl_str_mv Vivekananda, Umesh
Novak, Pavel
Bello, Oscar Daniel
Korchev, Yuri E.
Krishnakumar, Shyam S.
Volynski, Kirill E.
Kullmann, Dimitri M.
author Vivekananda, Umesh
author_facet Vivekananda, Umesh
Novak, Pavel
Bello, Oscar Daniel
Korchev, Yuri E.
Krishnakumar, Shyam S.
Volynski, Kirill E.
Kullmann, Dimitri M.
author_role author
author2 Novak, Pavel
Bello, Oscar Daniel
Korchev, Yuri E.
Krishnakumar, Shyam S.
Volynski, Kirill E.
Kullmann, Dimitri M.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CHANNELOPATHY
POTASSIUM CHANNEL
SYNAPTIC TRANSMISSION
topic CHANNELOPATHY
POTASSIUM CHANNEL
SYNAPTIC TRANSMISSION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Vivekananda, Umesh. University College London; Estados Unidos
Fil: Novak, Pavel. Queen Mary University Of London; Reino Unido
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
Fil: Korchev, Yuri E.. Imperial College London; Reino Unido
Fil: Krishnakumar, Shyam S.. University College London; Estados Unidos. University of Yale. School of Medicine; Estados Unidos
Fil: Volynski, Kirill E.. University College London; Estados Unidos
Fil: Kullmann, Dimitri M.. University College London; Estados Unidos
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/182836
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
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182836
identifier_str_mv 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
0027-8424
1091-6490
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/lookup/doi/10.1073/pnas.1608763114
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1608763114
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082741276246016
score 13.22299

Publicaciones similares