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Selective serotonin reuptake inhibitors potentiate anoctamin 6 activation (893.22)
Author(s) -
Nam Joohyun,
Kim Yung Kyu,
Lee Min Goo
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.893.22
Subject(s) - chemistry , serotonin , reuptake inhibitor , reuptake , patch clamp , pharmacology , fluoxetine , ion channel , neuroscience , biophysics , intracellular , paroxetine , electrophysiology , medicine , biology , biochemistry , receptor
Selective serotonin reuptake inhibitors (SSRIs) are a class of widely used antidepressants. The primary mechanism of action of these drugs involves the inhibition of the serotonin transporter (SERT or SLC6A4). In addition to the inhibition of the serotonin transporter, SSRIs also modulate a variety of ion channels including Ca 2+ ‐activated Cl − channels (CaCCs). Recently, anoctamins (ANOs) have been identified as a family of putative Cl − channels. Several research groups have reported that ANO6 generates outward‐rectifying Cl − currents by increasing intracellular Ca 2+ levels, which are activated after a delay of several minutes. However, the reason for the very slow activation of the Cl − current remains unexplained. Using the whole‐cell patch‐clamp technique, we examined the effects of SSRIs, including fluoxetine, paroxetine, and sertraline, on cloned human ANO6 expressed in HEK293 cells. In contrast to their inhibitory effect on ANO1, the SSRIs reduced the latency time for the activation of ANO6 currents in a concentration‐dependent manner and slightly enhanced the magnitude of the peak current resulting from ANO6 Ca 2+ ‐dependent activation. However, when we excised the membrane of the cells by using an inside‐out patch‐clamp technique we found that the ANO6 currents were inhibited by SSRIs. Although the exact mechanism by which the latency time of ANO6 activation is reduced remains unexplained, SSRIs might be involved in this ANO6 activation via an indirect pathway. ANO6 channels are involved in many physiological effects. Therefore, our study might contribute to a better understanding of the therapeutic action of SSRIs and their side effects. Grant Funding Source : This work was supported by a National Research Foundation of Korea (NRF, NO 2011‐0014404)