Harrow_1985_Pest.Sci_16_662

Intracellular current and voltage clamp techniques were used to investigate the mode of action of the anthelmintics, morantel, pyrantel and levamisole applied to the bag region of Ascaris suum muscle cells. Microperfusion of the anthelmintics and of O-acetylcholine (ACh) increased the input conductance and depolarised the membrane potential of the muscle bags. The relative potencies of these drugs were determined from dose-conductance relationships and found to be: morantel = pyrantel > levamisole > ACh. High doses (>10 uM) of morantel caused antagonism of ACh responses. ACh-induced currents were measured under voltage clamp (over the range -80 to +10mV). At membrane potentials between -80 and 0 mV, microperfusion of ACh induced a voltage-dependent inward current. The current-voltage relationship was linear for membrane potentials in the range -30 to +10mV. The reversal potential was measured directly and found to be about +10mV. The relationship became non-linear at membrane potentials more negative than -30 mV, and the degree of non-linearity was dependent upon the concentration of ACh. The current-voltage relationships for morantel, pyrantel and levamisole also possessed both linear (-30 to 0mV) and non-linear components. The reversal potential for each agonist, determined by extrapolation of the linear component of the current-voltage relationship, was approximately +10mV, indicating the same cation channels were activated both by ACh and the anthelmintics. Evidence for competition between ACh and pyrantel for the same membrane receptor was obtained using iontophoretic delivery of each agonist from a double-barrelled micropipette. It is concluded that the anthelmintics, morantel, pyrantel and levamisole act as potent agonists at ACh receptors on muscle bag membranes of A. suum.