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This Article Full Text Full Text (PDF) All Versions of this Article: 586/14/3325    most recent jphysiol.2008.153965v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Digby, G. J. Articles by Lambert, N. A. PubMed PubMed Citation Articles by Digby, G. J. Articles by Lambert, N. A. Related Collections Cellular

¹ Graduate Program in Neuroscience and Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, 30912, USA

Signalling by heterotrimeric G proteins is often isoform-specific, meaning certain effectors are regulated exclusively by one family of heterotrimers. For example, in excitable cells inwardly rectifying potassium (GIRK) channels are activated by Gβ dimers derived specifically from G_i/o heterotrimers. Since all active heterotrimers are thought to dissociate and release free Gβ dimers, it is unclear why these channels respond primarily to dimers released by G_i/o heterotrimers. We reconstituted GIRK channel activation in cells where we could quantify heterotrimer expression at the plasma membrane, GIRK channel activation, and heterotrimer dissociation. We find that G_oA heterotrimers are more effective activators of GIRK channels than G_s heterotrimers when comparable amounts of each are available. We also find that active G_oA heterotrimers dissociate more readily than active G_s heterotrimers. Differential dissociation may thus provide a simple explanation for G-specific activation of GIRK channels and other Gβ-sensitive effectors.

(Received 13 March 2008; accepted after revision 21 May 2008; first published online 22 May 2008)
Corresponding author N. A. Lambert: Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30809 USA. Email: nlambert{at}mcg.edu