The competitive nature of the action of acetylcholine and local anesthetics

Electrical characteristics of a monocellular electroplax preparation were recorded with intracellular electrodes. 1. 1.|Acetylcholine, carbamylcholine and neostigmine, activators of the receptor protein, rapidly and reversibly block electrical activity in low concentrations with simultaneous depolarization. Tetracaine, physostigmine, the tertiary analogue of neostigmine and curare, inhibitors of the receptor protein, block electrical activity without depolarizing the membrane. 2. 2.|The cell depolarized by acetylcholine is repolarized by curare even in the presence of acetylcholine. Both compounds act primarily on the synaptic membrane. The response to direct stimulation, as postulated by theory, is restored by curare even in the presence of acetylcholine. 3. 3.|In low concentration, 5·10 −5 M , physostigmine, due to its high affinity to cholinesterase, acts as an enzyme inhibitor. In high concentrations, 5·10 −3 M , physostigmine prevents depolarization due to acetylcholine through its action as a receptor inihibitor. 4. 4.|Tetracaine, in 2.5·10 −5 M , reverses the depolarizing action of acetylcholine 2.5·10 −6 M in the presence of the ester and physostigmine. The response to direct stimulation does not return in contrast to curare. 5. 5.|The depolizing action of carbamylcholine in 5·19 −5 M is also overcome by tetracaine 1·10 −4 M . On increasing the concentration of carbamylcholine to 5·10 −4 M the cell was again depolarized. 6. 6.|Puffer fish poison 7·10 −8 M blocks electrical activity by a non-competitive action without depolarization. Even in ten times higher concentration it does not prevent the depolarizing action of acetylcholine in its minumally active concentration.