Modified behavioral characteristics following ablation of the voltage-dependent calcium channel beta 3 subunit

Voltage-dependent calcium channels are important for calcium influx and the ensuing intracellular calcium signal in various excitable membranes. The beta subunits of these channels modify calcium currents through pore-forming alpha 1 subunits of the high-voltage- activated calcium channels. In the present study, beta 3 subunit-null mice were used to investigate the importance of the beta 3 subunit of the voltage-dependent calcium channel, which couples with the CaV2.2 ( alpha 1B) subunit to form the major component of neuronal N-type calcium channels in the brain. Western blot analysis revealed a significant decrease in N-type calcium channels in beta 3 subunit-null mice, while protein levels of other high-voltage-activated calcium channel alpha 1 subunits were unchanged. Immunoprecipitation analysis with an anti-CaV2.2 antibody showed that reshuffling of the assembly of N-type channels had occurred in the beta 3 subunit-null mice. Ablation of this subunit resulted in modified nociception, decreased anxiety, and increased aggression. The beta 3 subunit-null mice also showed impaired learning ability. These results suggest the importance of voltage-dependent calcium channels and the key role of the beta 3 subunit in memory formation, nociceptive sensory transduction, and various neurological signal transduction pathways.