Potassium homeostasis and its disorders

Disturbances in K+ balance are potentially life-threatening and occur under many circumstances. We propose to investigate how K+ homeostasis is regulated in the context of chronic kidney diseases (CKD). The occurrence of hyperkalemia is very frequent in CKD patients. Using nephrectomized mice, we work on providing a complete picture of K+ metabolism during CKD (hormones, fecal and renal K+ excretion, expression of K+ transporters in colon and kidney) and investigate whether increasing fecal K+ secretion (by inhibiting the colonic HKA2) could lower the risk of developing hyperkalemia. Regarding HKA2, little is known about the kinase-dependent regulatory pathways that regulate its expression level, intrinsic activity, cationic exchange mode, etc. Our aim is to investigate the effects of PKA, AMPK, SGK and NO pathways on HKA2-expressing oocytes either by using pharmacological approaches, or by co-expressing kinases (wild-type or mutated). Also, we currently perform functional studies on several HKA2 human polymorphisms we have identified, to determine if they may induce a change in HKA2 properties, thereby with possible consequences on potassium balance. The infection by Sars-Cov-2 leading to COVID-19 disrupts the potassium balance and we are investigating the mechanisms by which it infers with renal ion transport system.