Novel subunit composition of a renal epithelial KATP channel.
Unique ATP-inhibitable K+ channels (KATP) in the kidney determine the rate of urinary K+ excretion and play an essential role in extracellular K+ balance. Here, we demonstrate that functionally similar low sulfonylurea affinity KATP channels are formed by two heterologous molecules, products of Kir1.1a and cystic fibrosis transmembrane conductance regulator (CFTR) genes. Co-injection of CFTR and Kir1.1a cRNA into Xenopus oocytes lead to the expression of K+ selective channels that retained the high open probability behavior of Kir1.1a but acquired sulfonylurea sensitivity and ATP-dependent gating properties. Similar to the KATP channels in the kidney but different from KATP channels in excitable tissues, the Kir1.1a/CFTR channel was inhibited by glibenclamide with micromolar affinity. Since the expression of Kir1.1a and CFTR overlap at sites in the kidney where the low sulfonylurea affinity KATP are expressed, our study offers evidence that these native KATP channels are comprised of Kir1.1a and CFTR. The implication that Kir subunits can interact with ABC proteins beyond the subfamily of sulfonylurea receptors provides an intriguing explanation for functional diversity in KATP channels.
Ruknudin
A
A
Department of Physiology, Baltimore, Maryland 21201, USA.
Schulze
D H
DH
Sullivan
S K
SK
Lederer
W J
WJ
Welling
P A
PA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004594:Electrophysiology; D015870:Gene Expression / Q000235:genetics; D007668:Kidney / Q000502:physiology*; D008845:Microinjections; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000652:urine; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D018075:RNA, Complementary / Q000235:genetics; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D014981:Xenopus
D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018075:RNA, Complementary; D013453:Sulfonylurea Compounds; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011188:Potassium