Kir1.1 | ROMK1 I Potassium Voltage-Gated Channel Subfamily J Member 1
Family:
Inward-rectifier potassium ion channel
Subgroups:
Seven families channels demonstrate robust inward rectification: Kir1.1; Kir2.1 - Kir2.4; Kir3.1 - Kir3.4, Kir4.1 - Kir4.2; Kir5.1, Kir6.1 - Kir6.2; Kir7.1
Topology:
The channel protein contains two membrane spanning alpha helices denoted as M1 and M2. Four identical subunits form a functional homotetramer, heterotetramers can combine with members of the same subfamily
Kir1.1 Background Information
Kir1.1 is also known as ROMK (renal outer medullary potassion channel) or ATP-sensitive inward rectifier potassium channel 1. It is an ATP-dependent potassium channel that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb (TAL) and potassium secretion in the cortical collecting duct (CCD) of the nephron.
Gene:
KCNJ1
Human Protein:
UniProt P48048
Tissue:
Kidney and pancreatic islets, lower levels in skeletal muscle, pancreas, spleen, brain, heart and liver.
Function/ Application:
Plays a major role in potassium homeostasis in the kidney
Pathology:
Bartter syndrome 2, Antenatal Bartter Syndrome
Interaction:
Associated subunit: NHERF2 (Sodium-hydrogen exchange regulatory cofactor 2). Interacts with serum/glucocorticoid regulated kinase 1 (SGK1), Solute carrier family 9, subfamily A (SLC9A3R2/NHERF2), CFTR, WNK lysine deficient protein kinase 4, SH3 domain containing ring finger 1
Modulator:
Barium, ATP, glimepiride, glycodiazine, minoxidil, tolbutamide, glyburide, tertiapin-Q
Assays:
Patch clamp
Recommended Reviews:
Kubo et al. (2005) International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels. Pharmacol Rev 57(4):509-526
Testimonials
Prof. Dr. Jerod Denton - Statement about the Patchliner
"One of the biggest advantages of the Patchliner for our lab is that it enables students and fellows without formal training in patch clamp electrophysiology to begin generating meaningful data almost immediately. Instead of spending a couple of frustrating months learning the motor skills and hand-eye coordination necessary for conventional patch clamping with a microscope and micromanipulator, they spend that time designing and executing experiments, generating, evaluating and interpreting data and moving the project forward. The Patchliner also enables experimental flexibility that would be very difficult or impossible with conventional patch clamp rigs. For example, a talented undergraduate in the lab just finished up a series of intracellular drug application experiments. These studies would be difficult for the seasoned electrophysiologist and nearly impossible for an undergraduate student. However, the Patchliner allowed them to be completed in a very short period of time.
Another major advantage is that the Patchliner enables us to rapidly confirm or exclude hits from our primary fluorescence-based high-throughput screen using gold-standard electrophysiological methods. And the quality of the recordings rivals that of a conventional patch clamp rig. In fact, our first observations of pore "knock-off" of a new ROMK inhibitory small-molecule came from the Patchliner. These early observations from high-quality Patchliner recordings provided a clear direction for subsequent mutagenesis work aimed at defining the binding site of this molecule within the cytoplasmic channel pore."
Jerod S. Denton, Ph.D.,Assistant Professor of Anesthesiology and Pharmacology
Vanderbilt University Medical Center, Nashville, TN, USA
Publications
2011 - Development of a selective small-molecule inhibitor of Kir1.1, the Renal Outer Medullary Potassium Channel
Patchliner publication in Molecular Pharmacology (2011)
Authors:
Bhave G., Chauder B.A., Liu W., Dawson E.S., Kadakia R., Nguyen T.T., Lewis L.M., Meiler J., Weaver C.D., Satlin L.M., Lindsley C.W., Denton J.S.
2009 - High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1
Patchliner publication in Molecular Pharmacology (2009)
Authors:
Lewis L.M., Bhave G., Chauder B.A., Banerjee S., Lornsen K.A., Redha R., Fallen K., Lindsley C.W., Weaver C.D., Denton J.S.