Mechanism of Hypokalemia in Magnesium Deficiency

Mechanism for intracellular magnesium to decrease K⁺ secretion. A ROMK channel in the apical membrane of distal nephron is depicted. (A and B) At zero intracellular Mg²⁺, K⁺ ions move in or out of cell through ROMK channels freely depending on the driving force (i.e., not rectifying). At intra- and extracellular K⁺ concentrations of 140 and 5 mM, respectively, the chemical gradient drives K⁺ outward. An inside-negative membrane potential drives K⁺ inward. Inward and outward movement of K⁺ ions reach an equilibrium at −86 mV (i.e., equilibrium potential [E_K] = −60 × log 140/5). When membrane potential is more negative than E_K (e.g., −100 mV, a condition that rarely occurs in the apical membrane of distal nephron physiologically), K⁺ ions move in (influx; see A). Conversely, at membrane potential more positive than E_K (e.g., −50 mV, a physiologic relevant condition), K⁺ ions move out (see B). (C and D) At the physiologic intracellular Mg²⁺ concentration (e.g., 1 mM), ROMK conducts more K⁺ ions inward than outward (i.e., inward rectifying). This is because intracellular Mg²⁺ binds ROMK and blocks K⁺ efflux (secretion; see D). Influx of K⁺ ions displaces intracellular Mg²⁺, allowing maximal K⁺ entry (see C). This unique inward-rectifying property of ROMK places K⁺ secretion in the distal nephron under the regulation by intracellular Mg²⁺. Note that, though inward conductance is greater than outward, K⁺ influx (i.e., reabsorption) does not occur because of membrane potential more positive than EK.