Show simple item record

dc.creatorBrenes García, Oscar Gerardo
dc.creatorVandael, David Henry F.
dc.creatorCarbone, Emilio
dc.creatorMontarolo, Pier Giorgio
dc.creatorGhirardi, Mirella
dc.date.accessioned2020-08-06T16:26:35Z
dc.date.available2020-08-06T16:26:35Z
dc.date.issued2015
dc.identifier.citationhttps://www.sciencedirect.com/science/article/abs/pii/S0306452215009653?via%3Dihubes_ES
dc.identifier.issn0306-4522
dc.identifier.urihttp://hdl.handle.net/10669/81412
dc.description.abstractSynapsins (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.es_ES
dc.description.sponsorshipItalian Ministry of the University and Research/[PRIN 2009]//Italiaes_ES
dc.description.sponsorshipCompagnia di San Paolo/[]//Italiaes_ES
dc.language.isoen_USes_ES
dc.sourceNeuroscience, vol.311, pp.430-443es_ES
dc.subjectSynapsines_ES
dc.subjectInvertebrate neuronses_ES
dc.subjectCell excitabilityes_ES
dc.subjectCalcium channelses_ES
dc.subjectBK channelses_ES
dc.titleKnock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage-gated Ca2+ currents in Helix serotonergic neuronses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.identifier.doi10.1016/j.neuroscience.2015.10.046
dc.description.procedenceUCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicinaes_ES


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record