Role of receptor protein tyrosine phosphatase alpha (RPTPalpha) and tyrosine phosphorylation in the serotonergic inhibition of voltage-dependent potassium channels.
Pflugers Arch
; 441(2-3): 257-62, 2000 Dec.
Article
in En
| MEDLINE
| ID: mdl-11211111
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Serotonin
/
Protein Tyrosine Phosphatases
/
Receptors, Cell Surface
/
Phosphotyrosine
/
Potassium Channels, Voltage-Gated
/
Potassium Channel Blockers
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Pflugers Arch
Year:
2000
Document type:
Article