Is hydrogen ion (H+) the real second messenger in calcium signalling?

Most second messengers have the acknowledged ability to mobilize the segregated Ca2 + from intracellular stores, although the mechanisms of mobilization are unclear. To study this problem, the fact that inositol 1,4,5-trisphosphate, and six other known endogenous Ca2 + mobilizers are acids, or acid-generating compounds, is highlighted. In physiological conditions, a newly generated acid releases H+. The transient rise of H+ in the cytosol may induce the lowering of pH, mobilization of bound Ca2 +, protein conformational rearrangement, store depletion, and Ca2 + influx. Accordingly, a new description of the basic mechanism for signal transduction in non-excitable cells and the related consequences is put forward.