The effects of isoprenaline and a new beta-sympathomimetic amine upon spontaneous activity, diastolic depolarization and plateau height in cardiac Purkinje fibres.

1 In spontaneously active Purkinje fibres of young cows the dose-response curves of the action of isoprenaline upon different electrophysiological parameters were measured.2 The increase in slope of diastolic depolarization could roughly be described by a one-for-one binding curve with a half maximum effect near 10(-8) M and the increase in the height of the plateau level by a two-for-one binding curve with a half maximum effect near 10(-7) M (-)-isoprenaline.3 These dose-response curves were similar to those of two parameters measured under voltage clamp conditions by other authors. The increase in slope of diastolic depolarization behaved like the shift of the activation curve for the pacemaker potassium current towards positive potentials and the growth in plateau height like the increase in the slow inward current mainly carried by Ca ions. From this conformity we propose that the parameters evaluated by us from action potential records could be used for a qualitative analysis of the action of catecholamines on pacemaker potassium current and Ca influx.4 The effects of the isomers of a new drug, 1-isopropylamino-3(4'hydroxyphenoxy)-propan-2-ol (IHP), were evaluated in the same way as those of isoprenaline. The (-)-isomer was at optimal concentrations (10(-5) M) nearly half as effective as isoprenaline in increasing frequency and slope of diastolic depolarization but caused no increase in plateau height. An identical relationship, but at 5 to 10 times higher concentrations, was obtained with the (+)-isomer.5 When 10(-4) M(-)-IHP was added to a preparation equilibrated with a maximum dose of (-)-isoprenaline (10(-6) M), frequency and plateau height declined. This result together with the observation that the effects of IHP could be blocked by the specific beta-antagonist propranolol, revealed the beta-agonistic nature of the new drug. Its inefficiency in increasing the plateau height and thus the slow (Ca) inward current was explained by its relatively low potency and intrinsic activity.