ANTI-BETA-2 SUBUNIT ANTISENSE OLIGONUCLEOTIDES MODULATE THE SURFACE EXPRESSION OF THE ALPHA-1 SUBUNIT OF N-TYPE OMEGA-CTX SENSITIVE CA2+ CHANNELS IN IMR-32 HUMAN NEUROBLASTOMA-CELLS

High voltage activated Ca2+ channels are heteropolymeric complexes in which the alpha(1) subunit forms the channel, while the alpha(2)-delta and beta subunits are important for the assembly and regulation of the biophysical properties of the channel. We have tested the role of the beta(2) subunit on the expression and electrophysiological properties of the omega-conotoxin GVIA-sensitive Ca2+ channel expressed in the IMR 32 human neuroblastoma cell line. Anti-beta(2) subunit antisense oligonucleotides supplied to the cells in culture induced a time-dependent increase in the number of [I-125]-omega-conotoxin binding sites on the cell surface, which was not paralleled by an increase in current amplitude. We suggest that a reduction in the expression of beta(2) stimulates the transport to the plasma membrane of non-functioning Ca2+ channels and, in particular, of the alpha(1) omega-conotoxin binding subunit. (C) 1994 Academic Press, Inc.