Which ion has the highest intracellular concentration in most animal cells?
Ionic composition asymmetry between cytosol and extracellular fluid is actively established but reflects passive equilibrium for some ions. Primary determinant is Na+/K+ ATPase, P-type pump undergoing E1 to E2 transitions phosphorylating Asp369 in DKTGT motif, exporting three sodium and importing two potassium per ATP hydrolyzed. This creates extracellular sodium about 145 millimolar versus intracellular about 12 millimolar, and intracellular potassium about 140 millimolar versus extracellular 4 millimolar. Leak potassium channels dominated at rest maintain membrane potential near minus 90 millivolts close to EK. Chloride distribution about 110 millimolar outside versus 4 to 15 millimolar inside largely follows passive Donnan equilibrium set by impermeable anionic proteins and is modulated by K-Cl cotransporters. Calcium kept extremely low at 100 nanomolar cytosolic compared with 1 to 2 millimolar outside by SERCA sequestering into endoplasmic reticulum and PMCA extruding. Comparing abundant monovalents, potassium concentration highest inside cells, essential for enzyme activation, protein synthesis and volume regulation.
Ref: Lodish et al., Molecular Cell Biology, Section: Intracellular Ion Composition - Na+/K+ ATPase and K+ Dominance.