INTERACTIONS OF ANTICHOLINESTERASES WITH ACHATINA-FULICA ACETYLCHOLINE RESPONSES AND ELECTROGENIC SODIUM-PUMP

The dose-dependent effects of the anticholinesterases, neostigmine and mycotoxin territrem-B, were determined on: (i) Cl--responses of volta ge clamped Achatina fulica neurons to microperfused acetylcholine; (ii ) the 4 K+-induced outward currents evoked by an electrogenic sodium p ump in the same neuron; and (iii) acetylcholinesterase activity of Ach atina fulica ganglionic homogenates. Both compounds at low doses poten tiated the peak acetylcholine responses. However, they had different e ffects at higher (>1 mu M) doses in that neostigmine now antagonized a cetylcholine responses, while territrem-B still produced a maximal pot entiation. At all doses neostigmine produced a dose-dependent inhibiti on of acetylcholinesterase activity. The cholinolytic effect of high d oses of neostigmine was associated with the inhibition of 4 K+-induced current in the same neuron, while territrem-B neither altered the Kf- induced current nor antagonized acetylcholine responses. The cholinoly tic effect of neostigmine was completely antagonized by the inhibition of electrogenic sodium pump by ouabain or by perfusion with K+-free s olution. These results suggest that neostigmine at high concentrations inhibits the electrogenic sodium pump and that the cholinolytic effec t of high doses of neostigmine is secondary to this action. Territrem- B, on the other hand, had no effect on the electrogenic sodium pump an d had no effect on the neuronal membrane properties other than to inhi bit acetylcholinesterase. Thus, territrem-B may be a useful tool for s tudying the interaction between acetylcholinesterase and acetylcholine receptors.