Cooperative Effect of Certain Anaesthetics on the Lobster Giant Axon

Abstract

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 suggested^1,2 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 arguments^3–5 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 anaesthetics^8,9, 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 excitability^8–10—a hypothesis which also requires that non-ionizable alcohols play a different part.