Electrophysiological effects of aconitine in rat hippocampal slices.

The electrophysiological effects of aconitine were investigated in the rat hippocampal slice and compared with those of veratridine. Both alkaloids are known to bind at site 2 of sodium channels and to block its inactivation. Extracellular recordings revealed that aconitine and veratridine exert inhibitory effects on neuronal excitability. Aconitine slowly and reversibly decreased the population spike recorded in the CA1 pyramidal cell layer. The reduction of the spike amplitude was similar whether orthodromically or antidromically activated. The aconitine-induced inhibition did not differ from that of veratridine. However, following washout of aconitine, the amplitude of the antidromic spike was increased compared to the control amplitude. The veratridine-induced inhibition was only partially reversible. This inhibition was also observed during suppression of synaptic transmission by a low Ca2+/high Mg2+-medium, indicating an inhibition of axonal conductance. The results show that in the absence of synaptic transmission the antidromic (alvear) spike is more sensitive to the inhibitory action of aconitine than the presynaptic fiber spike elicited by stimulation of the Schaffer collaterals. Furthermore, it is shown that aconitine acts in an activity-dependent manner, in that the latency of onset of the inhibition is prolonged when the stimulation frequency is decreased. Field excitatory postsynaptic potentials were also suppressed by aconitine, whereas excitatory postsynaptic currents recorded by the patch clamp technique were not influenced by aconitine when cells were held at -60 mV.