Role of receptor protein tyrosine phosphatase alpha (RPTPalpha) and tyrosine phosphorylation in the serotonergic inhibition of voltage-dependent potassium channels.

Journal article

The activity of voltage-gated potassium (Kv) channels can be dynamically modulated by several events, including neurotransmitter-stimulated biochemical cascades mediated by G-protein-coupled receptors. By using a heterologous expression system, we show that activating the 5-HT2C receptor inhibits both Kv1.1 and Kv1.2 channels through a tyrosine phosphorylation mechanism. The major molecular determinants of channel inhibition were identified as two tyrosine residues located in the N-terminal region of the Kv channel subunit. Furthermore, we demonstrate that receptor protein tyrosine phosphatase alpha (RPTPalpha), a receptor protein tyrosine phosphatase, co-ordinates the inhibition process mediated via 5-HT2C receptors. We therefore propose that the serotonergic regulation of human Kv1.1 and Kv1.2 channel activity by the 5-HT2C receptor involves the dual coordination of both RPTPalpha and specific tyrosine kinases coupled to this receptor.

Authors: Imbrici, P; Tucker, S; D'Adamo, M; Pessia, M

• Publication status: Published
• Journal: Pflugers Archiv : European journal of physiology
• Volume: 441
• Issue: 2-3
• Pages: 257-262
• Publication date: 2000-12-01
• DOI: 10.1007/s004240000406
• EISSN: 1432-2013
• ISSN: 0031-6768
• Language: English
• Keywords: Mutagenesis, Site-Directed; Gene Expression; Genistein; Xenopus laevis; Potassium Channel Blockers; Potassium Channels, Voltage-Gated; Kv1.1 Potassium Channel; Kv1.2 Potassium Channel; Oocytes; Kinetics; Vanadates; Phosphotyrosine; Humans; Female; Enzyme Inhibitors; Phosphorylation; Potassium Channels; Transfection; Animals; Serotonin; Protein Tyrosine Phosphatases; Receptors, Cell Surface; Receptors, Serotonin; Receptor-Like Protein Tyrosine Phosphatases, Class 4