ION MOVEMENTS DURING VAGUS INHIBITION OF THE HEART 117 



was beating steadily at 24/min and the fractional loss of isotope per min 

 remained substantially constant in two successive control periods. After 

 admission of a fresh lot of wash solution the left vagus was stimulated for 

 7 min at 10/sec. This caused complete arrest for most of the time and an 

 almost threefold increase in the rate of outflow of ^'K. After the end of 

 stimulation tiie sinus soon resumed its beat and the rate of outflow of ^'^K 

 returned promptly to almost the initial value. Acetylcholine (2 < 10^'^ to 

 2 X 10'^ g/ml) produces a similar acceleration in the rate of loss of ^^K. 

 Differences in the timing of the application of acetylchohne, the duration of 

 the load period and season of the year had httle obvious influence on the 

 response, but a matter requiring attention is the exclusion of auricular tissue 

 from the preparation; for aUhough the auricles also show an increase in the 

 rate of ^-K efllux under the influence of acetylcholine (see, for instance, 

 Rayner and Weatherall, 1959) the effect is much smaller than in the sinus 

 venosus. 



The question may be asked whether the increase in the rate of outflow 

 observed could have arisen secondarily from a change in the electrochemical 

 driving force. In the present inhibitory situation the answer is fortunately 

 clear. During exposure to acetylcholine the preparation is arrested and the 

 inside of the fibres is more negative than the maximum negative potential 

 reached during diastole in the beating preparation (del Castillo and Katz, 

 1955, 1957; Hutter and Trautwein, 1955, 1956). The force driving potassium 

 out is therefore diminished at all times so an increase in the outflow rate 

 must be taken to signify an increase in permeability. The argument, in fact, 

 leads to the conclusion that the acceleration in the outflow of ^'-K produced 

 by acetylcholine might be greater could the attending arrest and hyper- 

 polarization be avoided. We have therefore made experiments in which the 

 wash solution contained enough potassium (c. 20 niM) to render the pre- 

 paration quiescent. Under these conditions acetylcholine usually produces 

 a considerably greater eff'ect than is observed when the wash solution contains 

 only 2-7 mM K (Fig. 2). 



Further evidence for an increase in potassium permeability by acetyl- 

 choline may be obtained by examining the influx of ^-K. One type of experi- 

 ment is illustrated in Fig. 3. Each block represents the amount of isotope 

 taken up by a tortoise sinus venosus in successive 5 min exposures to load 

 solution, the preparation itself being presented to the counter each time after 

 a 3 min wash in an inactive solution. It may be seen that during the fourth 

 and ninth 5 min periods, when the preparation was exposed to acetylcholine, 

 the uptake was considerably greater than during the control periods. Analysis 

 of the preparation at the end of the experiment showed that about 10% of the 

 tissue potassium had exchanged for tracer. This low degree of exchange was 

 probably due to the similar length of wash and load periods, and it accounts 

 for the relative constancy in the amounts of isotopes taken up in successive 



