Article thumbnail
Location of Repository

γ-Aminobutyric acid type B receptors are expressed and functional in mammalian cardiomyocytes

By Paco Lorente, Alain Lacampagne, Yvan Pouzeratte, Stephen Richards, Barbara Malitschek, Rainer Kuhn, Bernhard Bettler and Guy Vassort


γ-Hydroxybutyrate (GHB), an anesthetic adjuvant analog of γ-aminobutyrate (GABA), depresses cell excitability in hippocampal neurons by inducing hyperpolarization through the activation of a prominent inwardly rectifying K(+) (Kir3) conductance. These GABA type B (GABA(B))-like effects are clearly shown at high concentrations of GHB corresponding to blood levels usually reached during anesthesia and are mimicked by the GABA(B) agonist baclofen. Recent studies of native GABA(B) receptors (GABA(B)Rs) have favored the concept that GHB is also a selective agonist. Furthermore, cloning has demonstrated that GABA(B)Rs assemble heteromeric complexes from the GABA(B)R1 and GABA(B)R2 subtypes and that these assemblies are activated by GHB. The surprisingly high tissue content, together with anti-ischemic and protective effects of GHB in the heart, raises the question of a possible influence of GABA(B) agonists on excitable cardiac cells. In the present study, we provide electrophysiological evidence that GHB activates an inwardly rectifying K(+) current in rat ventricular myocytes. This effect is mimicked by baclofen, reversibly inhibited by GABA(B) antagonists, and prevented by pertussis toxin pretreatment. Both GABA(B)R1 and GABA(B)R2 are detected in cardiomyocytes by Western blotting and are shown to coimmunoprecipitate. Laser scanning confocal microscopy discloses an even distribution of the two receptors in the sarcolemma and along the transverse tubular system. Hence, we conclude that GABA(B)Rs are distributed not only in neuronal tissues but also in the heart, where they can be activated and induce electrophysiological alterations through G-protein-coupled inward rectifier potassium channels

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2000
OAI identifier:
Provided by: PubMed Central
Sorry, our data provider has not provided any external links therefore we are unable to provide a link to the full text.

Suggested articles

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.