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 [125I]-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.
Tarroni
P
P
Department of Medical Pharmacology, University of Milan, Italy.
Passafaro
M
M
Pollo
A
A
Popoli
M
M
Clementi
F
F
Sher
E
E
D000595:Amino Acid Sequence; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation; D020866:omega-Conotoxin GVIA
D015220:Calcium Channels; D016376:Oligonucleotides, Antisense; D010455:Peptides; D012333:RNA, Messenger; D020866:omega-Conotoxin GVIA; D002118:Calcium