Co-expression of sulfonylurea receptors and KATP channels in hamster insulinoma tumor (HIT) cells. Evidence for direct association of the receptor with the channel.
Cell membranes isolated from hamster insulinoma (HIT T15) cells at passages 65-74 contain high and low affinity receptors for a sulfonylurea derivative, 5-[125I]iodo,2-hydroxyglyburide (KD values of approximately 7 nM and 16 microM). Between passages 75 and 85, the estimated B(max) for the high affinity receptor decreases approximately 10-fold from approximately 1.6 to 0.16 pmol/mg membrane protein. By contrast, the density of low affinity binding sites, 800-1000 pmol/mg, is unaltered. The drop in high affinity receptors is paralleled by a decrease in the density of KATP channels assessed using patch-clamp and 86Rb(+)-efflux techniques. These results strongly support the idea that the high affinity sulfonylurea receptor is an integral part of the KATP channel.
Aguilar-Bryan
L
L
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Nichols
C G
CG
Rajan
A S
AS
Parker
C
C
Bryan
J
J
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000345:Affinity Labels; D000818:Animals; D001345:Autoradiography; D001692:Biological Transport; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D005905:Glyburide / Q000031:analogs & derivatives / Q000378:metabolism; D007340:Insulinoma / Q000378:metabolism*; D007457:Iodine Radioisotopes; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014407:Tumor Cells, Cultured
D018528:ATP-Binding Cassette Transporters; D000345:Affinity Labels; D007457:Iodine Radioisotopes; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; C064021:5-iodo-2-hydroxyglyburide; D000255:Adenosine Triphosphate; D012413:Rubidium; D005905:Glyburide