Acta Physiologica 2007; Volume 189, Supplement 653
The 86th Annual Meeting of The German Physiological Society
KIR2 POTASSIUM CHANNELS ARE DIFFERENTIALLY REGULATED BY GQ/11 COUPLED RECEPTORS
Abstract number: P05-L3-01
Fuchs1 L, Wischmeyer1 E
1Physiologisches Institut der Universitt Wrzburg
Inwardly rectifying potassium channels of the Kir2 subfamiliy are regulated by Gi/o-coupled (Wischmeyer & Karschin, 1996), as well as Gq/11-coupled receptors (Firth & Jones, 2001). So far, it is still under debate whether these receptors selectively target to different members of the Kir2 subfamily.
In order to investigate receptor induced inactivation cRNA of Kir2.12.4 together with acetylcholine M1, serotonin 5-HT2C, bradykinin B1 and B2 and histamine H1 receptors, respectively, was injected into Xenopus oocytes. Activation of the M1 receptor reduced the amplitude of Kir2.3 current by 38±5% (10 mM muscarine, n=5). In contrast, all other Kir2 subfamiliy members were not affected by the activation of coexpressed M1 receptors. The same was true for all other Gq/11-coupled receptors tested. None of them reduced Kir2 currents significantly. Further, we tried to find the structural basis of receptor-mediated inhibition of Kir2.3. In contrast to all other members of the Kir2 subfamily, Kir2.3 harbours a stretch of glycine residues within the extracellular loop between transmembrane region M1 and the pore region. However, mutating three of these glycine residues into alanines does not influence receptor-induced inhibition of Kir2.3.
Our results suggest that Kir2.3, but not Kir2.1, Kir2.2 and Kir2.4, is selectively inhibited via the muscarinic M1 receptor.
To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 189, Supplement 653 :P05-L3-01