Oxantel-activated single channel currents in the muscle membrane of Ascaris suum.
The patch clamp technique was used to investigate the action of the anthelmintic drug, oxantel, on nicotinic acetylcholine receptor (nAChR) currents recorded from vesicles of the somatic muscle cells of the nematode parasite Ascaris suum. The amplitudes of the currents were analysed at different membrane potentials to determine the single channel conductance. Also the open and closed durations were measured to determine the kinetic properties of the activated channel. Oxantel activated single nAChR currents throughout a concentration range 10-100 microM, these currents were not observed with oxantel-free pipette solutions. The mean open time of the activated channels at a membrane potential of -75 mV and a concentration of 10 microM was 1.34 ms. At higher concentrations the open times were shorter and voltage sensitive, decreasing in duration on hyperpolarization, thus suggesting open channel block. The kinetics were analysed using a simple channel block model. The forward block rate, K + B, increased with increasing oxantel concentration but showed little increase as the membrane was hyperpolarized. K + B was 2.41 x 10(7) M-1 s-1 at -50 mV and 2.64 x 10(7) M-1 s-1 at -100 mV. The unblocking rate constant, K-B, did exhibit voltage sensitivity being 443.6 s-1 at -50 mV and 86.8 s-1 at -100 mV. Thus the blocking dissociation constant KB (= K-B/K + B) was 18.5 microM at -50 mV and 3.3 microM at -100 mV. The simple channel block scheme was found to be insufficient to explain fully the observations made; reasons for this are discussed.
Dale
V M
VM
Department of Preclinical Veterinary Sciences, R. (D.) S. V. S. Summerhall, University of Edinburgh.
Martin
R J
RJ
D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D017165:Ascaris suum / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000502:physiology*; D018722:Nicotinic Agonists; D018408:Patch-Clamp Techniques; D011715:Pyrantel / Q000031:analogs & derivatives* / Q000494:pharmacology
D000969:Antinematodal Agents; D007473:Ion Channels; D018722:Nicotinic Agonists; D011715:Pyrantel; C003407:oxantel