Full-length and truncated Kv1.3 K+ channels are modulated by 5-HT1c receptor activation and independently by PKC
Autor: | K G Chandy, Jayashree Aiyar, Stephan Grissmer |
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Rok vydání: | 1993 |
Předmět: |
Serotonin
Potassium Channels Charybdotoxin Transcription Genetic Calmodulin Physiology G protein Scorpion Venoms Pertussis toxin Second Messenger Systems Piperazines Membrane Potentials RNA Complementary Mice Xenopus laevis Alkaloids 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Phorbol Esters Phosphoprotein Phosphatases Animals 5-HT5A receptor Virulence Factors Bordetella Cloning Molecular Protein kinase A Protein Kinase C Protein kinase C biology Calcineurin Cell Biology Isoquinolines Staurosporine Molecular biology Electric Stimulation Recombinant Proteins Cell biology Pertussis Toxin Guanosine 5'-O-(3-Thiotriphosphate) Receptors Serotonin Oocytes biology.protein Calmodulin-Binding Proteins Female Signal transduction Tyrosine kinase |
Zdroj: | American Journal of Physiology-Cell Physiology. 265:C1571-C1578 |
ISSN: | 1522-1563 0363-6143 |
Popis: | In T-cells, the Shaker-related gene, Kv1.3 encodes the type n K+ channel, whereas the type l channel is a product of the Shaw. subfamily gene, Kv3.1. Both these genes are also expressed in the brain. We have used the Xenopus oocyte heterologous expression system to study the modulatory effects of serotonin (5-hydroxytryptamine, 5-HT) on both these cloned channels. In oocytes coexpressing the mouse 5-HT1c receptor and mouse Kv1.3 channel, addition of 100 nM 5-HT causes a complete and sustained suppression of Kv1.3 currents in approximately 20 min. In contrast, 5-HT has no effect on mouse Kv3.1 currents when coexpressed with 5-HT1c receptor. The 5-HT-mediated suppression of Kv1.3 currents proceeds via activation of a pertussis toxin-sensitive G protein and a subsequent rise in intracellular Ca2+, but Ca2+ does not directly block the channel. Protein kinase (PK) C activation is not part of the pathway linking 5-HT1c receptor to Kv1.3 channels. However, phorbol esters independently suppress Kv1.3 currents. Deletion of the first 146 amino acids from the NH2-terminal, containing putative tyrosine kinase and PKA phosphorylation sites, does not alter the time course of 5-HT-mediated suppression of Kv1.3 currents, indicating that these residues are not necessary for modulation. Treatment of oocytes with calmodulin or phosphatase inhibitors does not alter 5-HT-mediated modulation. Collectively, these experiments indicate that the mouse Kv1.3 channel is capable of being modulated by 5-HT via 5-HT1c receptor in a G protein and Ca(2+)-dependent manner, but the subsequent steps in the pathway remain elusive.(ABSTRACT TRUNCATED AT 250 WORDS) |
Databáze: | OpenAIRE |
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