Agonist-evoked [Ca2+](i) oscillations have been considered a biophysical ph
enomenon reflecting the regulation of the IP3 receptor by [Ca2+](i). Here w
e show that [Ca2+](i) oscillations are a biochemical phenomenon emanating f
rom 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 a
ction disrupted agonist-evoked [Ca2+](i) oscillations by a stepwise convers
ion to a sustained response. Based on these findings and the effect of muta
nt RGS proteins and anti-RGS protein antibodies on Ca2+ signaling, we propo
se that RGS proteins within the G protein-coupled receptor complexes provid
e a biochemical control of [Ca2+](i) oscillations.