Re-examination of the effect of DFP on electrical and cholinesterase activity of squid giant axon.

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Abstract
The powerful irreversible inhibitor of cholinesterase, diisopropyl fluorophosphate (DFP), irreversibly blocks electrical activity of the squid (Loligo pealii) giant axon, but only in relatively high concentration. The experiments presented offer an explanation for the high concentration required. When C14-DFP is applied externally, radioactivity rapidly accumulates in the interior of the axon. However, the compound appearing in the axoplasm is not DFP, but its inactive hydrolysis product diisopropyl phosphoric acid. Both the axoplasm and, more importantly, the axonal envelope (membrane plus Schwann cell plus associated connective tissue) contain sufficient DFP hydrolyzing enzyme to account for the relatively high concentration of DFP required to block electrical activity.