Abstract
Kv3.1 channel is abundantly expressed in neurons and its dysfunction causes sleep loss, neurodegenerative diseases and depression. Fluoxetine, a serotonin selective reuptake inhibitor commonly used to treat depression, acts also on Kv3.1. To define the relationship between Kv3.1 and serotonin receptors (SR) pharmacological modulation, we showed that 1C11, a serotonergic cell line, expresses different voltage gated potassium (VGK) channels subtypes in the presence (differentiated cells (1C11D)) or absence (not differentiated cells (1C11ND)) of induction. Only Kv1.2 and Kv3.1 transcripts increase even if the level of Kv3.1b transcripts is highest in 1C11D and, after fluoxetine, in 1C11ND but decreases in 1C11D. The Kv3.1 channel protein is expressed in 1C11ND and 1C11D but is enhanced by fluoxetine only in 1C11D. Whole cell measurements confirm that 1C11 cells express (VGK) currents, increasing sequentially as a function of cell development. Moreover, SR 5HT1b is highly expressed in 1C11D but fluoxetine increases the level of transcript in 1C11ND and significantly decreases it in 1C11D. Serotonin dosage shows that fluoxetine at 10 nM blocks serotonin reuptake in 1C11ND but slows down its release when cells are differentiated through a decrease of 5HT1b receptors density. We provide the first experimental evidence that 1C11 expresses Kv3.1b, which confirms its major role during differentiation. Cells respond to the fluoxetine effect by upregulating Kv3.1b expression. On the other hand, the possible relationship between the fluoxetine effect on the kinetics of 5HT1b differentiation and Kv3.1bexpression, would suggest the Kv3.1b channel as a target of an antidepressant drug as well as it was suggested for 5HT1b.
Highlights
In the brain, the alternating activation of different ionic currents establishes the resting membrane potential, generates the action potential and regulates the neuronal firing frequency and neurotransmitter release, providing neuronal cells with specific electrical identity [1,2]
The present study provides evidence that fluoxetine affects Kv3.1b expression together with the secretion of serotonin during neuronal serotonergic 1C11 cell line development
We show for the first time the presence of the Kv3.1b channel in the 1C11 cell line previously defined as a neuronal serotonergic cell line [35]
Summary
The alternating activation of different ionic currents establishes the resting membrane potential, generates the action potential and regulates the neuronal firing frequency and neurotransmitter release, providing neuronal cells with specific electrical identity [1,2]. Kv3.1 is differentially regulated: antipsychotic treatment elevates the Kv3.1 level in the cortex but, in the hippocampus, chronic antidepressant drug use resulted in reduced activity of this channel [30]. For these reasons, we propose in this study to define the relationship between the expression of the Kv3.1b and the serotonergic activity of the 1C11 cell line, using fluoxetine, their common modulator. In vitro on the neuronal serotonergic cells line 1C11, that (1) the Kv3.1b channel is significantly expressed, (2) fluoxetine affects Kv3.1b expression but increases cell proliferation and enhances the expression of 5HT1b even in the absence of precursors and (3) Kv3.1b expression depends on the cell differentiation stage
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