A comparison of the electrophysiological effects of two organophosphates, mipafox and ecothiopate, on mouse limb muscles.
Adult male albino mice were given single subcutaneous injections of either mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7 and 28 days after dosing, in vitro electrophysiological measurements were carried out in the soleus and EDL. Action potentials and end-plate potentials were evoked at 30 Hz and recorded intracellularly from single muscle fibers. The amplitudes, time course, and latencies of these potentials were measured and the variability (jitter) of latencies was calculated. Recordings after mipafox were also made with 3-Hz stimulation. Acetylcholinesterase activity was inhibited by mipafox (65% in the soleus; 76% in the EDL) and ecothiopate (59% in the soleus; 42% in the EDL). Mipafox and ecothiopate both increased postjunctional (muscle action potential) jitter in the soleus and EDL at 7 days after dosing. Organophosphates caused an increase in end-plate potential amplitudes in the soleus. Mipafox caused an increase in prejunctional (end-plate potential) jitter at 28 days after dosing in both muscles. A single dose of ecothiopate also caused an increase in prejunctional jitter at 28 days in the soleus. The OP-induced increase in jitter was different at different frequencies of stimulation. The results show that there are electrophysiological changes in both muscles after administration of organophosphorus compounds. The slow-twitch soleus appears more sensitive to prejunctional changes caused by OPs than the fast-twitch EDL.
de Blaquière
G E
GE
Department of Environmental and Occupational Medicine, University of Newcastle upon Tyne, United Kingdom.
Williams
F M
FM
Blain
P G
PG
Kelly
S S
SS
D000110:Acetylcholinesterase / Q000032:analysis; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004456:Echothiophate Iodide / Q000008:administration & dosage / Q000633:toxicity*; D004558:Electric Stimulation; D006614:Hindlimb / Q000187:drug effects* / Q000502:physiology; D007279:Injections, Subcutaneous; D007531:Isoflurophate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology
D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; C005238:mipafox; D004456:Echothiophate Iodide; D000110:Acetylcholinesterase