Basic aspects of calcium chemistry and membrane interaction: on the messenger role of calcium.

To summarize the perspective developed in this lecture we begin by considering it as axiomatic: (1) that aqueous domains delimited by lipid membranes typify cellular structure; (2) that different compositions of extracellular and intracellular aqueous domains and differences among intracellular aqueous domains require selective permeation of lipid membranes; and (3) that inorganic ion movements across lipid membranes are a common denominator in permeation. This set of axioms lead to the following set of postulates: (1) Evolutionary solutions to the problematic apposition of ions and lipid barriers are fundamental aspects of cell function. (2) An effective messenger role for communication between aqueous domains requires (a) meticulous modulation of movement across lipid membranes and (b) selective interactions within aqueous domains. (3) An ion would be an effective messenger. In a search for an appropriate ionic messenger it is noted that inorganic cations have a wider range of interactions with biomolecules than anions, that the prevalent monovalent cations have too high a flux across lipid membranes and too weak an interaction with molecules in aqueous domains, that trivalent cations cannot as effectively be transported across lipid membranes, that divalent cation movement across lipid membranes can be well modulated and their divalent charge allows for a wide range of binding constants with biological molecules, and that for reasons of radius-compatibility with polypeptide chelation and due to the lack of stringent crystal field requirements, Ca2+ is a most suitable divalent cation for a messenger role.