Article

Evidence that Neuronal G-Protein-Gated Inwardly Rectifying K^+ Channels are Activated by Gbetagamma Subunits and Function as Heteromultimers

Division of Biology, California Institute of Technology, Pasadena 91225, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 07/1995; 92(14):6542-6546. DOI: 10.1073/pnas.92.14.6542
Source: PubMed

ABSTRACT Guanine nucleotide-binding proteins (G proteins) activate K^+ conductances in cardiac atrial cells to slow heart rate and in neurons to decrease excitability. cDNAs encoding three isoforms of a G-protein-coupled, inwardly rectifying K^+ channel (GIRK) have recently been cloned from cardiac (GIRK1/Kir 3.1) and brain cDNA libraries (GIRK2/Kir 3.2 and GIRK3/Kir 3.3). Here we report that GIRK2 but not GIRK3 can be activated by G protein subunits Gbeta_1 and Ggamma_2 in Xenopus oocytes. Furthermore, when either GIRK3 or GIRK2 was coexpressed with GIRK1 and activated either by muscarinic receptors or by Gbetagamma subunits, G-protein-mediated inward currents were increased by 5- to 40-fold. The single-channel conductance for GIRK1 plus GIRK2 coexpression was intermediate between those for GIRK1 alone and for GIRK2 alone, and voltage-jump kinetics for the coexpressed channels displayed new kinetic properties. On the other hand, coexpression of GIRK3 with GIRK2 suppressed the GIRK2 alone response. These studies suggest that formation of heteromultimers involving the several GIRKs is an important mechanism for generating diversity in expression level and function of neurotransmitter-coupled, inward rectifier K^+ channels.

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Available from: Paulo Kofuji, Jul 27, 2015
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