NOVEL SUBUNIT COMPOSITION OF A RENAL EPITHELIAL K-ATP CHANNEL

Unique ATP-inhibitable K+ channels (K-ATP) in the kidney determine the rate of urinary K+ excretion and play an essential role in extracellu lar K+ balance. Here, we demonstrate that functionally similar low sul fonylurea affinity K+, channels are formed by two heterologous molecul es, products of Kir1.1a and cystic fibrosis transmembrane conductance regulator (CFTR) genes. Go-injection of CFTR and Kir1.1a cRNA into Xen opus oocytes lead to the expression of K+ selective channels that reta ined the high open probability behavior of Kir1.1a but acquired sulfon ylurea sensitivity and ATP-dependent gating properties. Similar to the K+, channels in the kidney but different from K+, channels in excitab le tissues, the Kir1.1a/CFTR channel was inhibited by glibenclamide wi th micromolar affinity. Since the expression of Kir1.1a and CFTR overl ap at sites in the kidney where the low sulfonylurea affinity K-ATP ar e expressed, our study offers evidence that these native K-ATP, channe ls are comprised of Kir1.1a and CFTR. The implication that Kir subunit s can interact with ABC proteins beyond the subfamily of sulfonylurea receptors provides an intriguing explanation for functional diversity in K-ATP, channels.