UNASSIGNED: 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 @entity302 phenotypes and several mutations in @entity15735 genes have been associated with @entity302 in @entity1 and animal models. @entity15735 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 @entity302 . Another approach to investigate epileptogenic mechanisms is to understand how silencing @entity15735 affects the cellular behavior of single neurons and is associated with the hyperexcitable phenotypes observed in @entity302 . Here, we examined the functional effects of antisense-RNA inhibition of @entity15735 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 @entity141 and BK currents in @entity15735 -silenced cells seems to be related to changes in the shape of the AP waveform. These currents sustain the faster spiking in @entity15735 -deficient cells by increasing the after hyperpolarization and limiting the @entity4024 and @entity141 channel inactivation during repetitive firing. This in turn speeds up the depolarization phase by reaching the AP threshold faster. Our results provide evidence that @entity15735 silencing increases intrinsic cell excitability associated with increased @entity141 and @entity141 -dependent BK currents in the absence of excitatory or inhibitory inputs.

Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage-gated XXXX currents in Helix serotonergic neurons.

@entity1 :: ('9606', 'Species') :: ['humans'] @entity15735 :: ('23336', 'Gene') :: ['Syn'] @entity4024 :: ('D012964', 'Chemical') :: ['Na(+)'] @entity302 :: ('MESH:D004827', 'Disease') :: ['epileptic', 'epilepsy'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)']
@entity141 :: (CHEBI:29108,Chemical) :: ['Ca(2+)']
