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.