Brevetoxin modulates neuronal sodium channels in two cell lines derived from rat brain

Single Na+ channel currents were recorded from cell-attached membrane patch es from two neuronal cell lines derived from rat brain, B50 and B104, and c ompared before and after exposure of the cells to purified brevetoxin, PbTx -3. B50 and B104 Na+ channels usually exhibited fast activation and inactiv ation as is typical of TTX-sensitive Na+ channels. PbTx-3 modified channel gating in both cell lines. PbTx-3 caused (1) significant increases in the f requency of channel reopening, indicating a slowing of channel inactivation , (2) a change in the voltage dependence of the channels, promoting channel opening during steady-state voltage clamp of the membrane at voltages thro ughout the activation range of Na+ currents, but notably near the resting p otential of these cells (-60 - -50 mV), and (3) a significant, 6.7 mV hyper polarized shift in the threshold potential for channel opening. Na+ channel slope conductance did not change in PbTx-3-exposed 850 and B104 neurons. T hese effects of Pbx-3 may cause hyperexcitability as well as inhibitory eff ects in intact brain. (C) 1999 Intox Press, Inc.