Gating and selectivity of aconitine-modified sodium channels in neuroblastoma cells.
Currents through normal and aconitine-modified sodium channels in perfused neuroblastoma cells were measured under voltage-clamp conditions. Aconitine is shown to induce changes in channel selectivity so that channels become more permeable to NH4+ than to Na+. Aconitine induces the shift of voltage dependence of channel activation toward more negative potentials by about 20 mV. Aconitine-modified channels inactivate practically completely with a time-course similar to that for normal channels. Aconitine is effective when applied to either side of the membrane. Steady-state characteristics of the gating machinery of aconitine-modified channels are discussed in terms of three-state model. According to the model, aconitine increases the probability of finding the channel in open state, which is reflected in negative shift of the voltage dependence of activation. The model predicts that the larger this shift, the higher is the level of steady-state sodium conductance. The comparison of respective properties of aconitine-modified channels in neuroblastoma cell and frog nerve confirms this prediction. Aconitine is assumed to reach its receptor through the lipophilic part of the membrane.
D031841:Aconitum / Q000494:pharmacology*; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002999:Clone Cells; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D012964:Sodium