The idea that certain drugs and neurotransmitters produce their effects by combining with specific receptors was first clearly expressed by Langley (1905) on the basis of the selective and localized effect of nicotine on striated muscle fibres. In 1914, Langley published a paper in which the antagonism between ‘curari’ and nicotine was analysed and measured as the ratio by which the nicotine concentration had to be increased in order to produce a standard response in the presence of tubocurarine. It was clear that Langley had in mind the idea of competition between nicotine and curare for the receptor sites and it was surprising that he did not formulatethe theory quantitatively, particularly since Hill, working in Langley's laboratory in 1909, published a mathematical analysis of the action of nicotine on frog muscle giving kinetic and equilibrium equations based on the law of mass action, which could easily have been extended to give an account of competitive antagonism. Barger & Dale (1910) did not favour the idea of specific receptors for sympathomimetic amines.

It seems to be the membrane bound (Na++K +)-activated enzyme system which transforms the energy from a hydrolysis of ATP into a vectorial movement of sodium out and potassium into the cell against electrochemical gradients, i.e. this systems seems to be the transport system for sodium and potassium (see, for example, review by Skou, 1972; Hokin & Dahl, 1972).