THE FUNCTIONAL-ROLE OF MOLECULAR-FORMS OF ACETYLCHOLINESTERASE IN NEUROMUSCULAR-TRANSMISSION

The severity of poisoning following acetylcholinesterase (AChE) inhibi tion correlates weakly with total AChE activity. This may be partly du e to the existence of functional and non-functional pools of AChE. ACh E consists of several molecular forms. The aim of the present study wa s to investigate which of these forms will correlate best with neuromu scular transmission (NMT) remaining after partial inhibition of this e nzyme. Following sublethal intoxication of rats with the irreversible AChE inhibitor soman, diaphragms were isolated after 0.5 or 3 h. It ap peared that at 3 h after soman poisoning the percentage of G(1) increa sed, while those of G(4) and A(12) decreased. NMT was inhibited more s trongly than in preparations obtained from the 0.5 h rats with the sam e level of AChE inhibition, but with a normal ratio of molecular forms . NMT correlated positively with G(4) as well as with A(12), but inver sely with G(1). In vitro inhibition with the charged inhibitors DEMP a nd echothiophate resulted in higher levels of total AChE, relatively l ess G(1) and more G(4) and A(12) than after incubation with soman, but led to less NMT. Treatment of soman-intoxicated rats with the reactiv ating compound HI-6 resulted in preferential reactivation of A(12), pe rsisting low levels of G(1) and concurrent recovery of NMT as compared with saline-treated soman controls with equal total AChE activity. Ap parently, in rat diaphragm G(4) and A(12) are the functional AChE form s.