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Diisopropylfluorophosphate and Tetanic Stimulation Fail to Reverse Mecamylamine Antagonism of Renshaw Cells1
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Iowa State University Ames, Iowa 50011
Diisopropylfluorophosphate and Tetanic Stimulation Fail to Reverse Mecamylamine Antagonism of Renshaw Cells. VANMETER, W. G. (1984). Fundam. Appl. Toxicol. 4, S150–S155. Mecamylamine-induced antagonism of Renshaw cells was studied in the spinal cord of DIAL anesthetized adult male or spayed female mongrel cats. Renshaw cell unit responses to 1- or 2-Hz supramaximal antidromic stimulation of lumbar segment 7 ventral root were recorded by conventional means from glass micropipettes (2.7 M NaCl, tip diameter 1.0 to 1.6 µm, 2.0 to 4.0 M
resistance). Data were analyzed by computer. Mecamylamine (1.0 mg/kg iv) antagonizes the response to 1- or 2-Hz stimulation. The onset occurs within 60 sec, only the first one or two spikes remain after 2 min, and this antagonism is observed 30 min after injection. Persistence of action of acetylcholine (ACh) induced by diisopropylfluorophosphate (DFP 2.0 to 2.5 mg/kg iv) increases the spike frequency of the Renshaw cell burnt and reduces the variability in the number of spikes per discharge in response to 1- or 2-Hz antidromic stimulation. Excess ACh generated by 2 min of 20-Hz antidromic stimulation fails to reverse the mecamylamine-induced antagonism to 1- or 2-Hz antidromic stimulation. Also, DFP-induced persistence of action of ACh or 20-Hz (2 min) antidromic stimulation to induce excess ACh in the presence of DFP, fails to reverse the mecamylamine-induced antagonism of response to 1- or 2-Hz antidromic stimulation. It is concluded that the data agree with a mechanism of action of mecamylamine as a noncompetitive open channel blocker of the nicotinic receptor ion-channel complex which renders it nonresponsive to the agonist ACh and to the open channel blocker, DFP.