Reversibility of the Ca2+ channel alpha(1)-beta subunit interaction

The auxiliary beta subunit importantly regulates voltage-dependent Ca2+ cha nnel activity through an interaction with the AID domain, a binding site lo cated in the cytoplasmic I-II linker of the ion-conducting alpha (1) subuni t. In the present study, we used two synthetic peptides corresponding to pa rtial. sequences of the I-II linker of alpha (1A) (AID(A)-peptides) as tool s to disrupt the alpha (1)-beta interaction. In vitro binding experiments c onfirmed that these peptides exhibit a reasonable affinity to the neuronal beta (3) subunit to serve this purpose, although they failed to prevent imm unoprecipitation of native N- and P/Q-type channels by anti-beta (3) antibo dies. Together, our results (i) provide evidence for the reversibility of c hannel subunit association suggesting that the disruption of the alpha (1)- beta interaction may be a possible mechanism for Ca2+ channel regulation in vivo, and (ii) support a model whereby the alpha (1)-beta association is b ased on multiple interaction sites. (C) 2000 Academic Press.