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

Pflugers Arch. 2000 Dec;441(2-3):257-62. doi: 10.1007/s004240000406.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gene Expression
  • Genistein / pharmacology
  • Humans
  • Kinetics
  • Kv1.1 Potassium Channel
  • Kv1.2 Potassium Channel
  • Mutagenesis, Site-Directed
  • Oocytes / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism*
  • Potassium Channel Blockers*
  • Potassium Channels / genetics
  • Potassium Channels / physiology
  • Potassium Channels, Voltage-Gated*
  • Protein Tyrosine Phosphatases / physiology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • Receptors, Cell Surface*
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology
  • Serotonin / physiology*
  • Transfection
  • Vanadates / pharmacology
  • Xenopus laevis

Substances

  • Enzyme Inhibitors
  • KCNA1 protein, human
  • KCNA2 protein, human
  • Kv1.2 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Receptors, Cell Surface
  • Receptors, Serotonin
  • Kv1.1 Potassium Channel
  • Phosphotyrosine
  • Serotonin
  • Vanadates
  • Genistein
  • PTPRA protein, human
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4

Grants and funding