Molecular Mechanisms

Potassium Balance

In health, ROMK channels are precisely controlled to adjust urinary potassium excretion to match dietary potassium intake. Our early investigations revealed that membrane trafficking processes chiefly regulate ROMK in concert with physiological demands. Currently our funded studies center on elucidating the processes that drive ROMK internalization from the apical membrane, inspired by work from our lab and others that endocytosis of the channel safeguards against urinary potassium loss when dietary potassium or blood potassium are low and that exaggerated ROMK internalization contributes to high blood potassium in a familial disease of hyperkalemia.   We are building on our discoveries of novel endocytosis and recycling signals that are embedded within the ROMK structure; the intracellular machineries that decode the signals; and the signaling pathways that influence the interaction between the two.  Presently, we are dissecting the mechanisms in genetically engineered mice and in vitro model systems using modern molecular-cell biological methods, state-of-the art imaging techniques and physiological phenotyping. Our overarching goals are to provide novel insights into renal potassium handling in health and disease, and to identify pathways that are amenable to drug targeting for common disorders of potassium balance.  Funded by the National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases DK054231