Abstract
S100 Ca(2+)-binding proteins have been associated with a multitude of intracellular Ca(2+)-dependent functions including regulation of the cell cycle, cell differentiation, cell motility and apoptosis, modulation of membrane-cytoskeletal interactions, transduction of intracellular Ca(2+) signals, and in mediating learning and memory. S100 proteins are fine tuned to read the intracellular free Ca(2+) concentration and affect protein phosphorylation, which makes them candidates to modulate certain ion channels and neuronal electrical behavior. Certain S100s are secreted from cells and are found in extracellular fluids where they exert unique extracellular functions. In addition to their neurotrophic activity, some S100 proteins modulate neuronal electrical discharge activity and appear to act directly on ion channels. The first reports regarding these effects suggested S100-mediated alterations in Ca(2+) fluxes, K(+) currents, and neuronal discharge activity. Recent reports revealed direct and indirect interactions with Ca(2+), K(+), Cl(-), and ligand activated channels. This review focuses on studies of the physical and functional interactions of S100 proteins and ion channels.