The Potassium Switch

Potassium in Blood Pressure

The Welling lab, together with other members of the Foundation LeDucq Potassium in Hypertension Network of Excellence, helped define a pathway that explains why blood pressure is so sensitive to dietary potassium.  Its existence was first suggested when mutations in WNK kinases were identified as a cause of a genetic intolerance to sodium and potassium. Subsequent studies of our groups and others indicated that WNK kinases orchestrate a switch response that toggles the activities of distal nephron segments to maintain sodium and potassium balance over widely varied potassium intake. Because low potassium consumption, common in modern diets, presses pathway to conserve potassium at the expense of increasing sodium absorption, the switch mechanism explains how the modern diet feeds the fire of salt-sensitive hypertension. This highly collaborative program draws on the collective expertise of the entire team to rapidly accelerate the understanding of this new pathway.

A focus of the Welling lab in the network centers on elucidating how switch activation drives hypertension through structural remodeling of the distal nephron. RNAseq, cell lineage mapping, and molecule-to-systems phenotyping approaches are used to dissect the pathway in genetically engineered mouse models.  Results of these studies feed collaborative efforts to understand how the switch pathway operates from molecule to man.