beta Subunit heterogeneity in N-type Ca2+ channels

The beta subunit of the voltage-dependent Ca2+ channel is a cytoplasmic protein that interacts directly with an alpha(1) subunit, thereby modulating the biophysical properties of the channel. Herein, we demonstrate that the alpha(1) subunit of the N-type Ca2+ channel associates with several different beta subunits, Polyclonal antibodies specific for three different beta subunits immunoprecipitated I-125-omega-conotoxin GVIA binding from solubilized rabbit brain membranes, Enrichment of the N-type Ca2+ channels with an alpha(1B) subunit-specific monoclonal antibody showed the association of beta(1b), beta(3), and beta(4), subunits. Protein sequencing of tryptic peptides of the 57-kDa component of the purified N-type Ca2+ channel confirmed the presence of the beta(3) and beta(4) subunits. Each of the beta subunits bound to the alpha(1B) subunit interaction domain with similar high affinity. Thus, our data demonstrate important heterogeneity in the beta subunit composition of the N-type Ca2+ channels, which may be responsible for some of the diverse kinetic properties recorded from neurons.