---
_id: '1580'
abstract:
- lang: eng
text: Synapsins (Syns) are an evolutionarily conserved family of presynaptic proteins
crucial for the fine-tuning of synaptic function. A large amount of experimental
evidences has shown that Syns are involved in the development of epileptic phenotypes
and several mutations in Syn genes have been associated with epilepsy in humans
and animal models. Syn mutations induce alterations in circuitry and neurotransmitter
release, differentially affecting excitatory and inhibitory synapses, thus causing
an excitation/inhibition imbalance in network excitability toward hyperexcitability
that may be a determinant with regard to the development of epilepsy. Another
approach to investigate epileptogenic mechanisms is to understand how silencing
Syn affects the cellular behavior of single neurons and is associated with the
hyperexcitable phenotypes observed in epilepsy. Here, we examined the functional
effects of antisense-RNA inhibition of Syn expression on individually identified
and isolated serotonergic cells of the Helix land snail. We found that Helix synapsin
silencing increases cell excitability characterized by a slightly depolarized
resting membrane potential, decreases the rheobase, reduces the threshold for
action potential (AP) firing and increases the mean and instantaneous firing rates,
with respect to control cells. The observed increase of Ca2+ and BK currents in
Syn-silenced cells seems to be related to changes in the shape of the AP waveform.
These currents sustain the faster spiking in Syn-deficient cells by increasing
the after hyperpolarization and limiting the Na+ and Ca2+ channel inactivation
during repetitive firing. This in turn speeds up the depolarization phase by reaching
the AP threshold faster. Our results provide evidence that Syn silencing increases
intrinsic cell excitability associated with increased Ca2+ and Ca2+-dependent
BK currents in the absence of excitatory or inhibitory inputs.
article_processing_charge: No
article_type: original
author:
- first_name: Oscar
full_name: Brenes, Oscar
last_name: Brenes
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Emilio
full_name: Carbone, Emilio
last_name: Carbone
- first_name: Pier
full_name: Montarolo, Pier
last_name: Montarolo
- first_name: Mirella
full_name: Ghirardi, Mirella
last_name: Ghirardi
citation:
ama: Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. Knock-down of synapsin
alters cell excitability and action potential waveform by potentiating BK and
voltage gated Ca2 currents in Helix serotonergic neurons. Neuroscience.
2015;311:430-443. doi:10.1016/j.neuroscience.2015.10.046
apa: Brenes, O., Vandael, D. H., Carbone, E., Montarolo, P., & Ghirardi, M.
(2015). Knock-down of synapsin alters cell excitability and action potential waveform
by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons.
Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2015.10.046
chicago: Brenes, Oscar, David H Vandael, Emilio Carbone, Pier Montarolo, and Mirella
Ghirardi. “Knock-down of Synapsin Alters Cell Excitability and Action Potential
Waveform by Potentiating BK and Voltage Gated Ca2 Currents in Helix Serotonergic
Neurons.” Neuroscience. Elsevier, 2015. https://doi.org/10.1016/j.neuroscience.2015.10.046.
ieee: O. Brenes, D. H. Vandael, E. Carbone, P. Montarolo, and M. Ghirardi, “Knock-down
of synapsin alters cell excitability and action potential waveform by potentiating
BK and voltage gated Ca2 currents in Helix serotonergic neurons,” Neuroscience,
vol. 311. Elsevier, pp. 430–443, 2015.
ista: Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. 2015. Knock-down
of synapsin alters cell excitability and action potential waveform by potentiating
BK and voltage gated Ca2 currents in Helix serotonergic neurons. Neuroscience.
311, 430–443.
mla: Brenes, Oscar, et al. “Knock-down of Synapsin Alters Cell Excitability and
Action Potential Waveform by Potentiating BK and Voltage Gated Ca2 Currents in
Helix Serotonergic Neurons.” Neuroscience, vol. 311, Elsevier, 2015, pp.
430–43, doi:10.1016/j.neuroscience.2015.10.046.
short: O. Brenes, D.H. Vandael, E. Carbone, P. Montarolo, M. Ghirardi, Neuroscience
311 (2015) 430–443.
date_created: 2018-12-11T11:52:50Z
date_published: 2015-12-17T00:00:00Z
date_updated: 2025-09-23T09:25:46Z
day: '17'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuroscience.2015.10.046
external_id:
isi:
- '000366144000037'
file:
- access_level: open_access
checksum: af2c4c994718c7be417eba0dc746aac9
content_type: application/pdf
creator: dernst
date_created: 2020-05-15T06:50:20Z
date_updated: 2020-07-14T12:45:02Z
file_id: '7849'
file_name: 2015_Neuroscience_Brenes.pdf
file_size: 5563015
relation: main_file
file_date_updated: 2020-07-14T12:45:02Z
has_accepted_license: '1'
intvolume: ' 311'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
page: 430 - 443
publication: Neuroscience
publication_status: published
publisher: Elsevier
publist_id: '5591'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Knock-down of synapsin alters cell excitability and action potential waveform
by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 311
year: '2015'
...