Abstract
Stargazin, a transmembrane protein expressed in the nervous system, shares similarities with the γ1 subunit of skeletal muscle calcium channels. It was thus termed γ2 subunit of neuronal calcium channels. Stargazin downregulates the expression of CaV2 channels, however, its functional modulation of these channels remains debated. We have reported that Stargazin modulates CaV2.2 channel by a Gβγ-dependent mechanism and suggested that Stargazin is not a true subunit of this channel, since all its effects on channel function are dependent on the presence of Gβγ. Moreover, Stargazin also modulated the GIRK channel in a Gβγ-dependent fashion. Here we report that Gβγ-dependent modulation by Stargazin of the biophysical properties of CaV2.2 is unrelated to its negative effect on channel expression and current amplitude. Finally, we suggest that this Gβγ dependent modulation of Stargazin may have physiological relevance, since it was still present when we used Ca2+ as charge carrier, instead of Ba2+