Further characterization of regulation of Ca(V)2.2 by stargazin

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 Ca(V)2 channels, however, its functional modulation of these channels remains debated. We have reported that Stargazin modulates Ca(V)2.2 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 Ca(V)2.2 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(+).