Abstract
5-hydroxytryptamine-4 (5-HT 4) receptors have been proposed to contribute to the generation of atrial fibrillation in human atrial myocytes, but it is unclear if these receptors are present in the hearts of small laboratory animals (e.g. rat). In this study, we examined presence and functionality of 5-HT 4 receptors in auricular myocytes of newborn rats and their possible involvement in regulation of gap junctional intercellular communication (GJIC, responsible for the cell-to-cell propagation of the cardiac excitation). Western-blotting assays showed that 5-HT 4 receptors were present and real-time RT-PCR analysis revealed that 5-HT 4b was the predominant isoform. Serotonin (1 μM) significantly reduced cAMP concentration unless a selective 5-HT 4 inhibitor (GR113808 or ML10375, both 1 μM) was present. Serotonin also reduced the amplitude of L-type calcium currents and influenced the strength of GJIC without modifying the phosphorylation profiles of the different channel-forming proteins or connexins (Cxs), namely Cx40, Cx43 and Cx45. GJIC was markedly increased when serotonin exposure occurred in presence of a 5-HT 4 inhibitor but strongly reduced when 5-HT 2A and 5-HT 2B receptors were inhibited, showing that activation of these receptors antagonistically regulated GJIC. The serotoninergic response was completely abolished when 5-HT 4, 5-HT 2A and 5-HT 2B were simultaneously inhibited. A 24 h serotonin exposure strongly reduced Cx40 expression whereas Cx45 was less affected and Cx43 still less. In conclusion, this study revealed that 5-HT 4 (mainly 5-HT 4b), 5-HT 2A and 5-HT 2B receptors coexisted in auricular myocytes of newborn rat, that 5-HT 4 activation reduced cAMP concentration, I Ca L and intercellular coupling whereas 5-HT 2A or 5-HT 2B activation conversely enhanced GJIC.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.