The 5‐HT4 receptor subtype inhibits K+ current in colliculi neurones via activation of a cyclic AMP‐dependent protein kinase

• Published in: British journal of pharmacology Vol. 105; no. 4; pp. 973 - 979
• Main Authors: Fagni, L., Dumuis, A., Sebben, M., Bockaert, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.1992
• Subjects: 5‐HT4 receptor; 5‐Hydroxytryptamine; Animals; Cells, Cultured; Cyclic AMP - pharmacology; Enzyme Activation - drug effects; K+ current; Mice; neuronal plasticity; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons - drug effects; Neurons - metabolism; patch‐clamp; Potassium - metabolism; Protein Kinases - metabolism; Receptors, Serotonin - classification; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Serotonin - pharmacology; Superior Colliculi - drug effects; Superior Colliculi - metabolism
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1992.tb09087.x

1 The aim of the present study was to examine the effect of 5‐hydroxytryptamine (5‐HT) on K+ current in primary culture of mouse colliculi neurones and to identify the 5‐HT receptor subtype that could be involved in this effect. 2 The voltage‐activated K+ current of the neurones was partially blocked by 8‐bromo adenosine 3′:5′‐cyclic monophosphate (8‐bromo‐cyclic AMP). This effect was mimicked by 5‐HT and the action of 5‐HT could be antagonized by H7, a non specific protein kinase inhibitor, and by PKI, the specific cyclic AMP‐dependent protein kinase blocker. 3 A similar cyclic AMP‐dependent blockade of the K+ current was found with renzapride (BRL 24 924) and other 5‐HT4 receptor agonists such as cisapride, BIMU 8, zacopride and 5‐methoxytryptamine (5‐MeOT). ICS 205 930, the classical 5‐HT4 receptor blocker, could not be used in this study because it inhibited the studied K+ current by itself. However, the novel 5‐HT4 receptor antagonist, DAU 6285 blocked the effects of 5‐HT and renzapride on the K+ current. 4 The current was insensitive to the 5‐HT1 and 5‐HT3 receptor agonists (8‐hydroxy‐2‐(di‐n‐propylamino) tetralin, RU 24 969, carboxamidotryptamine, 2‐CH3‐5‐HT) as well as to 5‐HT1, 5‐HT2 and 5‐HT3 antagonists (methiothepin, ketanserin, ondansetron [GR 38 032]). Moreover, these antagonists did not affect the actions of the tested 5‐HT4 receptor agonists. 5 The present results show that part of the voltage‐activated K+ current in mouse colliculi neurones is cyclic AMP‐sensitive and the blockade of the current by 5‐HT involves the 5‐HT4 receptor subtype. The putative implication of 5‐HT4 receptors in neuronal plasticity, via a blockade of K+ channels, is discussed.