Molecular model for receptor-stimulated calcium spiking.

• DOI: 10.1073/pnas.85.14.5051
• Publication Date: 2006-05-31T10:38:36Z
• Authors: T Meyer; L Stryer
• Keywords: Second messenger system; Calcium pump; Calcium Signaling; Calcium ATPase

Many cells exhibit periodic transient increases in cytosolic calcium levels rather than a sustained rise when stimulated by hormone or growth factor. We propose here molecular model that accounts for spiking induced constant stimulus. Four elements give to repetitive transients: cooperativity and positive feedback between pair of reciprocally coupled (crosscoupled) messengers, followed deactivation then reactivation. The crosscoupled messengers our are inositol 1,4,5-trisphosphate (InsP3) ions. opening channels the endoplasmic reticulum binding multiple molecules InsP3 provides required cooperativity. stimulation receptor-activated phospholipase C released ions leads feedback. is destroyed phosphatase, ion pumped back into reticulum. These processes generate bistability: concentration abruptly from basal level at threshold degree activation C. Spiking further requires slow subsequent In model, mitochondrial sequestration prevents increasing above several micromolar enables system return state. When store refilled critical Ca2+-ATPase pump, cooperative InsP3-gated channel begins again next spike. time reach sets interval spikes. amplitude, shape, period spikes calculated this like those observed experimentally.