Antisense depletion of β-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 α 1 subunits. These channels share a common structure with an α 1 subunit associated with at least two regulatory subunits ( β, α 2– δ). Any of the six α 1-related channels identified to date are regulated in their functional properties through an interaction with the ancillary β-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 β-subunit, like HVA channels, is unknown. To address this issue, we have used an antisense strategy to inhibit β-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 β-antisense, while HVA currents were drastically decreased. Since LVA Ca channel currents in NG 108-15 cells are not regulated by β-subunits, it is reasonable to postulate that the pore-forming subunit(s) of these channels lacks an interaction domain with a β-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.