COOPERATIVE EFFECT OF CERTAIN ANAESTHETICS ON LOBSTER GIANT AXON

ANAESTHETICS which reversibly block electrical activity in nerves can be used as chemical probes to provide information about the dynamic processes which occur during the nerve impulse. Interpretation of this information requires an understanding of the relevant physical interactions responsible for the action of these substances on the cell membrane. It has frequently been suggested1,2 that the classical, ionizable, local anaesthetics, such as procaine, act on the excitable membrane by a different set of rules than do the non-ionizable anaesthetics such as the alcohols. This hypothesis resulted from arguments3-5 that the cationic forms of the local anaesthetics are directly responsible for blockage of electrical activity. These arguments contrast with earlier conclusions6 and have recently been questioned by Strobel and Bianchi7. Observations of interactions between phospholipids, calcium ions and the classical local anaesthetics8,9, and the effect of raised calcium concentration on procaine block10, have been used to support the hypothesis that competitive interaction of local anaesthetics for calcium binding sites is responsible for block of excitability8-10 - a hypothesis which also requires that non-ionizable alcohols play a different part. © 1969 Nature Publishing Group.