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

Most second messengers have the acknowledged ability to mobilize the segregated Ca(2+) 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 Ca(2+) 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 Ca(2+), protein conformational rearrangement, store depletion, and Ca(2+) influx. Accordingly, a new description of the basic mechanism for signal transduction in non-excitable cells and the related consequences is put forward.