Serotonin regulates gap junction coupling in the developing rat somatosensory cortex.
To further elucidate the role of the neuromodulatory transmitter serotonin (5-HT) during early postnatal development of the neocortex, we investigated the effects of 5-HT on gap junction coupling in the somatosensory cortex of rats aged between postnatal days 7 and 10. The gap junction-permeable tracer neurobiotin was injected into single neurons via microelectrodes or patch pipettes. Under control conditions, clusters of about 25 tracer-coupled neurons were observed. Serotonin reduced dye-coupling between lamina II/III pyramidal cells in a concentration-dependent and reversible manner. The 1,4,5-inositol triphosphate (IP3) receptor antagonist heparin as well as the protein kinase C inhibitor NPC 15437 suppressed the uncoupling action of 5-HT, suggesting that the serotonergic effect involved IP3 receptor-mediated release of calcium ions from intracellular stores. In contrast, the 5-HT-induced reduction in gap junction coupling was not antagonized by Rp-adenosine-3',5'-cyclic monophosphothionate, an inhibitor of cAMP dependent protein kinase. The uncoupling effect of 5-HT was mimicked by 5-HT2 receptor agonists and antagonized by the 5-HT2 receptor antagonist ritanserin, indicating that 5-HT suppressed gap junction coupling via activation of 5-HT2 class receptors. Our results suggest that the developmental functions of 5-HT not only involve the modulation of chemical synaptic transmission but also include the regulation of the gap junctional communication system during differentiation of the neocortex.
Rörig
B
B
Department of Physiology, University of Munich, Germany.
Sutor
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B
D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D008297:Male; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000254:growth & development / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013873:Thionucleotides; C070614:neurobiotin; C016957:adenosine-3',5'-cyclic phosphorothioate; D012701:Serotonin; D001710:Biotin; D006493:Heparin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases