Inhibitory effects on L- and N-type calcium channels by a novel Caβ variant identified in a patient with autism spectrum disorder.

Voltage-gated calcium channel (VGCC) subunits have been genetically associated with autism spectrum disorders (ASD). The properties of the pore-forming VGCC subunit are modulated by auxiliary β-subunits, which exist in four isoforms (Caβ). Our previous findings suggested that activation of L-type VGCCs is a common feature of Caβ subunit mutations found in ASD patients. In the current study, we functionally characterized a novel Caβ variant (p.R296C) identified in an ASD patient. We used whole-cell and single-channel patch clamp to study the effect of Caβ on the function of L- and N-type VGCCs. Furthermore, we used co-immunoprecipitation followed by Western blot to evaluate the interaction of the Caβ-subunits with the RGK-protein Gem. Our data obtained at both, whole-cell and single-channel levels, show that compared to a wild-type Caβ, the Caβ variant inhibits L- and N-type VGCCs. Interaction with and modulation by the RGK-protein Gem seems to be intact. Our findings indicate functional effects of the Caβ variant differing from that attributed to Caβ variants found in ASD patients. Further studies have to detail the effects on different VGCC subtypes and on VGCC expression.