title: Effect of adrenaline on mechanical activity and electrical events in frog ventricle
Creators: name: Graham, John Alistair
Publisher: name: University of Glasgow
Year: 1966

description: 1. Experiments were carried out to examine the effect of adrenaline on mechanical activity and electrical events in frog ventricular muscle. 2. Mechanical activity was observed in a superfused preparation, which has the advantage over other preparations that the ionic environment of all the cells can be quickly altered. 3. Resting and action potentials of individual cells under various conditions were measured using intracellular microelectrodes. 4. The effect of adrenaline on chloride flux across the cell membrane was examined using the radio-isotope of chloride, 36Cl. 5. When the tissue is exposed to Ringer containing excess KCl, there is a rapid depolarisation of the cells leading to development of a contracture. There is a characteristic relationship between developed tension and the logarithm of the external potassium concentration or the membrane potential. 6. Adrenalire reduced the contracture tension developed for each concentration of potassium tested. the average reduction being 37.5%. This reduction was not due to the spike of tension which preceded development of the contracture tension after adrenaline. 7. There was no change of the adrenaline effect on contracture tension when the chloride of the Ringer was replaced with sulphate. 8. Adrenaline also reduced the contracture tension developed when the tissue was exposed to sodium-free Ringer. 9. Adrenaline hyperpolarised the membrane of the ventricular cells; this was found in normal Ringer, Ringer containing excess KCl and sodium-free Ringer. 10. The effect of adrenaline is to change the relationship between contracture tension and membrane potential for each concentration of excess potassium along the slope of the curve joining the pre-adrenaline plots. This suggests that the effect of adrenaline on contracture tension may be mediated through the effect on the membrane potential, such that the new increased potential after adrenaline only allows development of the smaller amount of tension which would be expected according to the tension/potential relationship. 11. Ouabain in toxic doses blocks the hyperpolarising action of adrenaline, in the presence of ouabain the membrane is depolarised by exposure to adrenaline. 12. The beta-blocking agent pronethalol could block the effect of adrenaline on twitch, contracture and membrane potential. 13. It is postulated that the hyperpolarisation of the cell membrane by adrenaline may be due to an increased activity of the 'electrogenic' sodium pump. 14. The effect of adrenaline on the action potential of frog ventricular cells was to give an increase in the magnitude of the overshoot and to increase the duration of the action potential. This effect was dose-dependent. 15. It was found that this effect on the action of the external fluid, being greater at low values of the ratio. The effect was also greater at each value of the ratio when the ventricle was stimulated potential was dependent on the [Ca++]/[Na+]2 at a low rate (2/min) instead of the usual 15/min. 16. Adrenaline increased the conduction velocity of the tissue, the effect being more marked when the external Ca++ concentration was high. 17. It was noted that during the course of an experiment the twitch in normal Ringer decreased quickly as hypodynamia developed; however the twitch in the presence of adrenaline remained constant throughout. 18. This effect of adrenaline on the twitch tension was also found to be affected by the ratio [Ca++]/[Na+]2 the perfusing Ringer. The percentage increase in twitch tension after adrenaline was greater at low values of the ratio and the time taken to produce the maximum effect was prolonged under these conditions. 19. In normal Ringer adrenaline produced a variable change in the time to peak twitch tension. However, at low [Ca++]/[Na+]2 ratios, adrenaline gave a constant prolongation of the time to peak tension, and vice versa. When the ventricle was stimulated at 2/min adrenaline gave a prolongation of the time to peak was tension even when the ratio [Ca++]/[Na+]2 was twice normal. 20. The results presented above are thought to cast some doubt on the view commonly held that the time to peak twitch tension can be taken as a measure of the duration of the action potential. 21. Experiments with 36Cl have failed to show any change in chloride flux across the membrane during exposure of the tissue to adrenaline. 22. In the light of the results given above an attempt is made to explain the action of adrenaline on twitch tension and action potential on an ionic basis, and a postulated scheme of the action is given in the Discussion.