RGS proteins provide biochemical control of agonist-evoked [Ca2+]i oscillations

Agonist-evoked [Ca2+](i) oscillations have been considered a biophysical phenomenon reflecting the regulation of the IP3 receptor by [Ca2+](i). Here we show that [Ca2+](i) oscillations are a biochemical phenomenon emanating from regulation of Ca2+ signaling by the regulators of G protein signaling (RGS) proteins. [Ca2+](i) oscillations evoked by G protein-coupled receptors require the action of RGS proteins. Inhibition of endogenous RGS protein action disrupted agonist-evoked [Ca2+](i) oscillations by a stepwise conversion to a sustained response. Based on these findings and the effect of mutant RGS proteins and anti-RGS protein antibodies on Ca2+ signaling, we propose that RGS proteins within the G protein-coupled receptor complexes provide a biochemical control of [Ca2+](i) oscillations.