Clinical importance of potassium intake and molecular mechanism of potassium regulation

Introduction Potassium (K+) intake is intrinsically linked to blood pressure. High-K+ intake decreases hypertension and associated lower mortality. On the other hand, hyperkalemiacauses sudden death with fatal cardiac arrhythmia and is also related to higher mortality. Renal sodium (Na+)–chloride (Cl‒) cotransporter(NCC), expressed in the distal convoluted tubule, is a key molecule in regulating urinary K+ excretion. K+ intake affects the activity of the NCC, which is related to salt-sensitive hypertension. A K+-restrictive diet activates NCC, and K+ loading suppresses NCC. Hyperpolarization caused by decreased extracellular K+ concentration ([K+]ex) increases K+ and Cl‒ efflux, leading to the activation of Cl‒-sensitive with-no-lysine (WNK) kinases and their downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NCC.