Gβγ induces Ca 2+ influx from the extracellular space. SK-Mel-2 cells were subjected to Ca 2+ signal measurements. a and b) SK-Mel-2 cells were incubated with L9A (20 μM) or mSIRK (20 μM) followed by 8-pMeOPT stimulation (200 μM). mSIRK, but not L9A, increased Ca 2+ signal. 8-pMeOPT failed to show an additional increase of Ca 2+ signal after mSIRK. c, d and e) mSIRK-induced Ca 2+ signal was inhibited by pretreatment with GDPβS (100 μM) for 5 min (c), by Ca 2+ removal from the media (d) or by depletion of Ca 2+ in the extracellular space with EGTA (5 mM) (e). SK-Mel-2 cells were subjected to Ca 2+ signal measurements. f, g and h) Inhibition of IP3 receptors with 2-APB (1 μM) (f) or xestopongin C (1 μM) (g), and blocking of ryanodine receptor with ryanodine (10 μM) (h), did not inhibit mSIRK-induced Ca 2+ elevation. i) mSIRK increases Ca 2+ signal SK-Mel-2 cells after depletion of Ca 2+ in the ER with thapsigargin (2 μM).