Caveolin-3 negatively regulates recombinant cardiac K(ATP) channels.
We have recently shown that ATP-sensitive potassium (K(ATP)) channels in the heart are localized in the caveolae of cardiac myocytes and regulated by caveolae-related signaling. However, little is known about the role of caveolins, signature proteins of caveolae, in cardiac K(ATP) channel function. The present study was designed to explore the potential functional interaction between caveolin-3 and K(ATP) channels. The cardiac K(ATP) channel subunits Kir6.2 and SUR2A were transiently transfected in HEK293T cells with or without co-transfection of caveolin-3 or caveolin-1. Our data demonstrated that the recombinant K(ATP) channel activity in HEK293T cells was inhibited by expression of caveolin-3, but not caveolin-1. The application of caveolin-3 scaffolding domain peptide, corresponding to amino acid residues 55-74 of caveolin-3, blocked the inhibitory effect of caveolin-3 on K(ATP) channels. However, the same peptide did not have any significant effect on K(ATP) channels in HEK293T cells without caveolin-3 expression. We further confirmed that K(ATP) channels co-immunoprecipitated with caveolin-3 but not caveolin-1. The association of K(ATP) channels with caveolin-3 was largely prevented by caveolin-3 scaffolding domain peptide. Our results indicate that caveolin-3 negatively regulates Kir6.2/SUR2A channel function.
Garg
Vivek
V
Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Sun
Wei
W
Hu
Keli
K
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051244:Caveolin 3 / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D047468:Immunoprecipitation; D009206:Myocardium / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D051244:Caveolin 3; D020110:Pinacidil; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577510:ABCC9 protein, human