Changes in Ca2+ channel expression upon differentiation of SN56 cholinergic cells

The SN56 cell line, a fusion of septal neurons and neuroblastoma cells, has been used as a model for central cholinergic neurons. These cells show inc reased expression of cholinergic neurochemical features upon differentiatio n, but little is known about how differentiation affects their electrophysi ological properties. We examined the changes in Ca2+ channel expression tha t occur as these cells undergo morphological differentiation in response to serum withdrawal and exposure to dibutyryl-cAMP. Undifferentiated cells ex pressed a T-type current with biophysical and pharmacological properties si milar, although not identical, to those reported for the current generated by the alpha (1H) (CaV3.2) Ca2+ channel subunit. Differentiated cells expre ssed, in addition to this T-type current, high voltage activated currents w hich were inhibited 38% by the L-type channel antagonist nifedipine, (5 muM ), 37% by the N-type channel antagonist omega -conotoxin-GVIA (1 muM), and 15% by the P/Q-type channel antagonist omega -agatoxin-IVA (200 nM). Curren t resistant to these inhibitors accounted for 15% of the high voltage activ ated current in differentiated SN56 cells. Our data demonstrate that differ entiation increases the expression of neuronal type voltage gated Ca2+ chan nels in this cell line, and that the channels expressed are comparable to t hose reported for native basal forebrain cholinergic neurons. This cell lin e should thus provide a useful model system to study the relationship betwe en calcium currents and cholinergic function and dysfunction. (C) 2001 Else vier Science B.V. All rights reserved.