Antisense depletion of beta-subunits fails to affect T-type calcium channels properties in a neuroblastoma cell line.
Voltage-gated calcium channels can be classified into high voltage activated (HVA) and low voltage activated (LVA or T-type) subtypes. The molecular diversity of HVA channels primarily results from different genes encoding their pore-forming alpha1 subunits. These channels share a common structure with an alpha1 subunit associated with at least two regulatory subunits (beta, alpha2-delta). Any of the six alpha1-related channels identified to date are regulated in their functional properties through an interaction with the ancillary beta-subunit. By contrast, the diversity and the molecular identity of LVA or T-type calcium channels have yet to be defined. Whether LVA channels are modulated by a beta-subunit, like HVA channels, is unknown. To address this issue, we have used an antisense strategy to inhibit beta-subunit expression in the NG 108-15 neuroblastoma cell line. Differentiated NG 108-15 cells express both LVA and HVA channels. We found that LVA currents were unaffected when cells were incubated with beta-antisense, while HVA currents were drastically decreased. Since LVA Ca channel currents in NG 108-15 cells are not regulated by beta-subunits, it is reasonable to postulate that the pore-forming subunit(s) of these channels lacks an interaction domain with a beta-subunit (AID). This molecular feature, which is common to various T-type channels, indicates further that LVA calcium channels belong to a channel family structurally distant from HVA channels.
Institut de Génétique Humaine (UPR 1142), Montpellier, France.
V
V
Leuranguer
E
E
Bourinet
P
P
Lory
J
J
Nargeot
D000818:Animals; D015220:Calcium Channels / Q000737:chemistry*; D005910:Glioma; D051379:Mice; D009447:Neuroblastoma; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D020319:Oligodeoxyribonucleotides, Antisense