Differential modulation of cardiac potassium channels by Grb adaptor proteins.
Scaffolding growth factor receptor-bound (Grb) adaptor proteins are components of macromolecular signaling complexes at the plasma membrane and thus are putative regulators of ion channel activity. The present study aimed to define the impact of Grb adaptor proteins on the function of cardiac K(+) channels. To this end channel proteins were coinjected with the adaptor proteins in Xenopus oocytes and channel activity analyzed with two-electrode voltage-clamp. It is shown that coexpression of Grb adaptor proteins can reduce current amplitudes of coexpressed channels. Grb7 and 10 significantly inhibited functional currents generated by hERG, Kv1.5 and Kv4.3 channels. Only Grb10 significantly inhibited KCNQ1/KCNE1 K(+) channels, and only Grb7 reduced Kir2.3 activity, whereas neither Grb protein significantly affected the closely related Kir2.1 and Kir2.2 channels. The present observations for the first time provide evidence for a selective and modulatory role of Grb adaptor proteins in the functional expression of cardiac K(+) channels.
Physiologisches Institut 1, University Tuebingen, Tuebingen, Germany.
Oana N
ON
Ureche
Liviu
L
Ureche
Ulrike
U
Henrion
Nathalie
N
Strutz-Seebohm
Florian
F
Bundis
Klaus
K
Steinmeyer
Florian
F
Lang
Guiscard
G
Seebohm
D000818:Animals; D051383:GRB10 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D051382:GRB7 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D009865:Oocytes; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014982:Xenopus laevis
D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D051382:GRB7 Adaptor Protein; D051383:GRB10 Adaptor Protein