Effects of organophosphorus agents on sarcoplasmic reticulum in skinned skeletal muscle fibers.
These experiments were designed to determine whether skinned skeletal muscle fibers could be useful in screening new antidotes to organophosphorus poisons. Isometric force and fiber diameter were measured in mechanically skinned fibers from mice and frogs. Fibers were depleted of calcium and placed in a calcium loading solution that contained 0.5 mM EGTA with pCa 6.25. The elapsed time (zero time) before a contracture began and the maximum rate of force development (slope) were measured and divided by the square of the diameter (normalized zero time, normalized slope). The zero time was assumed to be the time required for the sarcoplasmic reticulum to attain a threshold concentration for calcium-induced calcium release, and the slope was assumed to indicate primarily the rapidity of the release of calcium from the sarcoplasmic reticulum. Organophosphorus agents, sarin, soman, tabun, and VX were also placed in the loading solutions. Only sarin failed to shorten the normalized zero times of mouse fibers compared to controls, and all agents decreased the normalized slopes. The normalized zero times of frog fibers were not altered by the agents, but the normalized slopes were altered by some agents. Pralidoxime chloride (PAM) and 3-Cl-2,5,6-trimethylbenzoic acid (TBA) were also added to the loading solution for mouse fibers; PAM was marginally effective in moderating some actions of the organophosphates. Because the effects of the agents on the fibers were so definite, we concluded that the skinned muscle fiber might indeed be useful as a screening tool for developing and testing new antidotes to organophosphorus poisons.
Mobley
B A
BA
Department of Physiology and Biophysics, University of Oklahoma, College of Medicine, Oklahoma City 73190.
Beesley
R C
RC
Reddy
Y S
YS
Johnson
J L
JL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D009132:Muscles / Q000187:drug effects*; D009943:Organophosphorus Compounds; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011894:Rana pipiens; D012519:Sarcoplasmic Reticulum / Q000187:drug effects*
D007306:Insecticides; D009943:Organophosphorus Compounds; D011220:Pralidoxime Compounds; C028797:pralidoxime; D002118:Calcium