The kinetics of the transfer of alkali metal ions between an assembly of cells, such as make up a muscle, and the surrounding medium depend on two factors, the rate of diffusion of the ions in the extra-cellular space and the rate of crossing the cell boundaries. Equations describing the time course of the process have been solved for the special cases of sodium and potassium ions being transferred into the cells of a thin sheet of muscle.The transfer of the sodium ion takes place as if it were the sum of diffusion and permeation processes. From experimental data it was possible to deduce the diffusion constant of the ion in the extra-cellular space (2.6 x 10-6 cm.2 sec.-l), the cell permeability (0.0005 cm. hr. -l), the fraction of extra-cellular space (0*1-0*3), and the ratio of the internal to the external sodium concentration (0-I 4-0-28).The potassium ion transfer involves both diffusion and permeability constants implicitly ; by assuming a diffusion constant the permeability constant was obtained (0.0034 cm. hr.-l). This permeability constant was found to be independent of the concentration of KC1 in the Ringer's solution in the range 0.015 yo KCl t o 0.09 yo. KCl. The effect of loss of potassium from the cells on the permeability is discussed.

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The work described in this paper is a continuation of observations already made in this laboratory on the antidiuretic action of nicotine (Burn, Truelove, and Burn, 1945; Walker, 1948). Taylor and Walker (1951) have recently shown that the action is followed by the appearance of an antidiuretic substance in the urine of man resembling in its properties the posterior lobe hormone and not nicotine.If a man drinks water, the onset of diuresis indicates the arrest of the normal secretion of antidiuretic hormone. When posterior lobe extract is injected intravenously at this point, inhibition of the diuresis occurs and lasts for a time depending on the amount injected. We have determined the dose-response relationship in three subjects. We have also estimated the proportion of antidiuretic hormone excreted in the urine after the intravenous injection of posterior lobe extract in varying amounts. A few experiments have been done in which the antidiuretic response to nicotine (either inhaled in tobacco smoke or injected) has been determined, and the amount of antidiuretic hormone excreted has been measured. METHODSThe observations were made on three male subjects in the afternoon. Each of them emptied his bladder every 15 minutes and recorded the volume. In certain experiments in which the antidiuretic effect was expected to be small, this period was reduced to 5 minutes. At the beginning of an experiment, the subject was required to show that he was not already very hydrated by producing two volumes, each of less than 25 ml. Then he drank one litre of water in 1-2 minutes. About 45 minutes later, when the volume of urine produced in the previous 15 minutes was more than 70 ml., the injection was given, or, in some experiments, the smoking was begun. The diuresis was then usually inhibited for a varying time, after which it increased to reach a second peak. The urine output was recorded until this peak was passed.The pituitary (posterior lobe) extract (PLE) was prepared by British Drug Houses, Ltd. Nicotine was injected as a solution of nicotine hydrogen tartrate in saline. This salt contains one-third by weight of nicotine base. All injections were made intravenously. The doses were usually contained in 0.5 ml., except the large doses of PLE and nicotine, which were in 1 ml.

The uptake of labelled noradrenaline by isolated rabbit atria has been studied, and the rate of outflow of radioactivity after a period of loading has been recorded. There is first a rapid outflow presumably from extracellular space, followed by a slow outflow presumably from intracellular space. Cocaine greatly diminished the intracellular uptake. Tyramine caused an increased outflow of radioactivity from intracellular sites which was not due to the increase in atrial rate, since noradrenaline which increased the rate more than tyramine had less effect on the outflow.In order to study the uptake of noradrenaline by isolated rabbit atria, observations have been made using noradrenaline containing '4C, which was sent to us by Dr. McChesney Goodall. The atria were prepared from rabbits of 1.5 to 2.0 kg body weight as described in the preceding paper by Azarnoff and Burn (1961). When the atria were set up in the bath for about 1 hr and were observed to be contracting normally, the labelled noradrenaline was added to the fluid in the bath and was allowed to act for-about 75 min. The bath was then emptied and the fluid was replaced and the rate of loss of radioactivity from the atria was determined. The effect of cocaine, of tyramine and of noradrenaline on this rate of outflow of radioactivity was observed. METHODSThe labelled noradrenaline was in solution in sealed glass ampoules and was (±)-[2-'4C] noradrenaline, the radioactivity being 9.5 ,C per ml. The concentration of DL-noradrenaline was 80.3 /ug per ml.In the various experiments the amounts of noradrenaline solution added to the 5 ml. bath varied from 0.1 to 0.3 ml. The noradrenaline was allowed to act for 75 min, after which time the bath was emptied. Five ml. of solution without noradrenaline was put in the bath and removed after 5 min. This procedure of emptying and filling the bath was repeated at varying intervals for 3 to 4 hr. All fluid removed from the bath was assayed for radioactivity by drying down a small aliquot on a planchette and counting in a windowless counter. No correction was made for self-absorption, the aliquot always having the same volume. At least 1,000 counts were recorded. RESULTSCourse of loss of radioactivity. The results in one experiment (Table 2, Expt. 13) were as follows. When the atria were set up in the bath at 320 C, they were beating

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