Heterologously expressed serotonin 1A receptors couple to muscarinic K+ channels in heart

Andreas Karschin*, Begonia Y. Ho, Cesar Labarca, Orna Elroy-Stein, Bernard Moss, Norman Davidson, Henry A. Lester

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In cardiac atrial cells, muscarinic acetylcholine receptors activate a K+ current directly via a guanine nucleotide-binding protein (G protein). Serotonin type 1A receptors may activate a similar pathway in hippocampal neurons. To develop a system in which receptor/G protein/K+ channel coupling can be experimentally manipulated, we have used a highly efficient recombinant vaccinia virus vector system to express human serotonin 1A receptors in primary cultures of rat atrial myocytes. The expressed 1A receptors activated the inwardly rectifying K+ conductance that is normally activated by the endogenous muscarinic acetylcholine receptors. Maximal responses to either agonist occluded further activation by the other agonist. The average activation time constants for serotonin were about 5 times slower than for acetylcholine. The data support suggestions that the intracellular signaling pathway from seven-helix receptors to G proteins and directly to ion channels is widespread in excitable cells. After a fraction of the G proteins are activated irreversibly by guanosine 5′-[γ-thio]triphosphate, subsequent transduction proceeds more efficiently. One possible interpretation is that multiple G-protein molecules are required to activate each channel. Vaccinia virus expression vectors are thus useful for expressing seven-helix receptors in primary cultures of postmitotic cells and have provided a heterologous expression system for the signaling pathway from seven-helix receptors to G proteins and directly to ion channels.

Original languageEnglish
Pages (from-to)5694-5698
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number13
DOIs
StatePublished - 1 Jul 1991
Externally publishedYes

Keywords

  • Acetylcholine
  • Atrial cells
  • Guanine nucleotide-binding proteins
  • Seven-helix receptors
  • Vaccinia virus expression

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