Hebert Laboratory

ATP-sensitive and ATP regulated potassium channels

Movement of ions through channels is governed by conformational changes resulting in channel opening or closing, also referred to as gating. Ion channels have evolved an array of gating sensors. We study how nucleotides and protons gate inwardly rectifying K channels. We had cloned the initial member of this inward-rectifier channel family in 1993. These K channels play vital roles in kidney, heart, vascular smooth muscle, and pancreatic beta-cells and loss of function mutations result in severe renal, cardiovascular, pancreatic and CNS disorders.

Representative publications:

Ho, K., Nichols, C.G., Lederer, W.J., Lytton, J., Vassilev, P.M., Kanazirska, M.V., and Hebert, S.C.: Cloning and expression of an inwardly rectifying ATP-regulated potassium channel. Nature, Article, 1993; 362: 31-38.

Vanoye, C.G., MacGregor, G.G., Dong, K., Tang, L.-Q., Hall, A.E., Lu, M., Giebisch, G. and Hebert, S.C.: The carboxy-termini of KATP channels bind nucleotides. J. Biol. Chem. 2002; 277:23260-23270.

Lu, M., Wang, T., Yan, Q., Yang, X., Dong, K., Knepper, M.A., Wang, W., Giebisch, G., Shull G.E., and Hebert, S.C.: Absence of small-conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartterís) knockout mice. J. Biol. Chem. 2002; 277: 37881-37887.

Dong, K., Tang, L.-Q., MacGregor, G.G., Vanoye, C.G. and Hebert, S.C.: Localization of the ATP-binding site to a 39 amino acid region of the COOH-terminus of the ATP-sensitive K+ channel, Kir1.1. J. Biol. Chem. 2002; 277:49366-49373.

Lu, M., Hebert, S.C. and Giebisch, G.: Hydrolyzable ATP and PIP2 modulate small-conductance K+ channel in the apical membrane of rat cortical collecting duct (CCD). J. Gen Physiol. 2002; 120:603-615.

MacGregor, G.G., Dong, K., Vanoye, C.G., Tang, L.-Q., Giebisch, G. and Hebert, S.C.: Nucleotides and phospholipids compete for binding to the C-terminus of KATP channels. Proc. Natl. Acad. Sci., U.S.A., 2002; 99: 2726-2731.

Lie-qi Tang, Ke Dong, Gordon MacGregor, Qiang Leng, Anthony O'Connell