Research Awards Recipients

Lay Summary

Cells are the living units of all organisms. Each unit corresponds to a fluid-filled space that is contained by a lipid envelop (also called surface membrane), and within the fluid itself, there are many additional fluid-filled spaces that are also contained within lipid envelops. These envelops are naturally impermeable to molecules. However, they must be able to allow the passage of such molecules in a very controlled manner so that cells can maintain a normal function. They achieve such a task through the presence of various transport proteins that are designed to allow the movement of very specific molecules. It is for these reasons that transport proteins come into several varieties that each play a very precise and exclusive role based on the types of molecules that must be transported and the types of cells where they must be present.

One of the transport systems that is involved in molecule exchanges across cellular membranes is known to catalyze the movement of potassium (K) along with chloride (Cl) simultaneously: it is thus called the K-Cl cotransporter system. This protein has also been shown to catalyze the movement of hydrogen (H) along with Cl. Through these various functions, the K-Cl cotransporter system allows all cells to maintain their ion and water content, and it enables specialized cells, those included in the kidney's filtration systems (called nephrons), to control how much of these ions are retained or excreted by the kidney. It is thus not surprising that the renal K-Cl cotransporter system has been shown to play a role in blood pressure control and to regulate urinary acid excretion.

Humans possess 4 different types of K-Cl cotransporters (KCCs) that belong to a larger family of proteins called cation-Cl cotransporters (CCCs). Not surprisingly, each type of KCC exerts its role in a relatively unique way, but we still do not know exactly how. Dr. Isenring project proposes to decipher the precise role and localization of the KCCs in the nephron and gain insight into some of the mechanisms by which humans regulate their salt and acid base balance as well as their blood pressure. Such studies could thus lead to the identification of new targets for the treatment or prevention of disorders that are very common in the general population. 

We already know of human syndromes that are due to abnormalities in the operation of ion transporters and that manifest as renal salt-losing disorders with or without low blood pressure or as renal salt-retaining disorders with or without high blood pressure. Importantly, these studies will help understand how abnormal K-Cl cotransport leads to various manifestations and will have to be carry out before any new drugs are generated. Otherwise, researchers will not know precisely which of the KCCs should be targeted and how these transporters should be altered to generate beneficial effects.