--- _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: 2021-01-12T06:51:44Z day: '17' ddc: - '570' department: - _id: PeJo doi: 10.1016/j.neuroscience.2015.10.046 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' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 311 year: '2015' ...