| 1.Research Institution | Osaka University | |
| 2.Research Area | Life Science | |
| 3.Research Field | Cellular Signaling | |
| 4.Term of Project | FY1996〜FY2000 | |
| 5.Project Number | 96L00302 | |
| 6.Title of Project | The Regulation of K+ Channel Activity by G Protein |
| Name | Institution,Department | Title of Position |
| Yoshihisa, Kurachi | Osaka University, Graduate School of Medicine | Professor |
8.Core Members
| Names | Institution,Department | Title of Position |
| Atsushi, Inanobe | Osaka University, Graduate School of Medicine AssistantProfessor | |
| Masayuki, Tanemoto | Osaka University, Graduate School of Medicine | Assistant Professor |
9.Cooperating Researchers
| Names | Institution,Department | Title of Position |
| Kiyoshi, Inageda | Osaka University, Graduate School of Medicine | Research Associate |
| Satoru, Fujita | Osaka University, Graduate School of Medicine | Research Associate |
10.Summary of Research Results
|
In native cardiac myocytes, there is a time-dependence to the G protein-gated inwardly rectifying K+ (KG) channel current during voltage steps which accelerates as the concentration of acetylcholine is increased. This phenomenon has been called 'relaxation' and is not reproduced in the reconstituted Kir3.1/Kir3.4 channel in Xenopus oocytes. We revealed that RGS4, a regulator of G protein signaling, restores relaxation to the reconstituted Kir3.1/Kir3.4 channel (Fujita et al., J. Physiol., 526.2, 587-592, 2000). We further examined the mechanism of this phenomenon by expressing various combinations of membrane receptors, G proteins, Kir3.0 subunits and mutants of RGS4 in Xenopus oocytes (Inanobe et al., J. Physiol., in press). RGS4 restored relaxation to KG channels activated by the pertussis toxin (PTX)-sensitive G protein-coupled m2-muscarinic receptor but not to those activated by the Gs protein-coupled β2-adrenergic receptor. RGS4 induced relaxation not only in heteromeric KG channels composed of Kir3.1 and Kir3.4 but also in homomeric assemblies of either an active mutant of Kir3.1 (Kir3.1/F137S) or an isoform of Kir3.2 (Kir3.2d). Truncation mutants of RGS4 showed that the RGS domain itself was essential to reproduce the effect of wild-type RGS4 on the KG channel. The mutation of residues in the RGS domain which interact with the α subunit of the G protein (Gα) impaired the effect of RGS4. These results indicates that interaction between the RGS domain and PTX-sensitive Gα subunits mediates the effect of RGS4 on the agonist concentration-dependent relaxation of KG channels. |
11.Key Words
(1)Potassium channel、(2)G protein、(3)RGS protein
12.References
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