(A) Density of Ca²⁺ ions (red mesh) and Na⁺ ions (blue mesh) around the hTPC2 protein matrix from simulations performed in equimolar dicationic solution. Left: side view; right: view from the lumen. (B) Interactions of Na⁺ and Ca²⁺ ions with water oxygen atoms (blue) and protein oxygen atoms (red) within their first solvation shell. The main interaction sites with hTPC2 at the SF, central cavity (Cav), and hydrophobic gate (HG) are marked. Na⁺ ions show closer interactions with the protein, especially at the SF and in the central cavity, and a higher degree of desolvation.