IDENTIFICATION OF A CALCIUM-CHANNEL MODULATOR USING A HIGH-THROUGHPUTYEAST 2-HYBRID SCREEN

The interaction of the N-type calcium channel beta 3 subunit with the alpha 1B subunit alters the activation/inactivation kinetics and the m aximal conductance of the channel. The defined protein-protein interac tion of the human alpha 1B and beta 3 subunits provides a target for s mall-molecule modulation of N-type channel activity. We describe a hig h throughput screen based on a counterselection yeast two-hybrid assay , which was used to identify small molecules that disrupt alpha 1B-bet a 3 subunit interactions and Inhibit N-type calcium channel activity. These small molecules may be a new class of calcium channel antagonist s with therapeutic potential.