Further characterization of regulation of Ca_V2.2 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_V2 channels, however, its functional modulation of these channels remains debated. We have reported that stargazin modulates Ca_V2.2 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_V2.2 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 Ba ²⁺.