RELATION BETWEEN THE CURRENT UNDERLYING PACEMAKER ACTIVITY AND BETA-ADRENOCEPTORS IN CARDIAC PURKINJE-FIBERS - STUDY USING ADRENALINE, PROCAINE, ATENOLOL AND PENBUTOLOL

The pacemaker current - iK2 - in cardiac Purkinje fibres was analysed using the voltage clamp technique described by Deck et al. (1964). (-)-Adrenaline (5.5 · 10-6 M) causes the wellknown shift of the Hodkin-Huxley kinetics in the depolarizing direction. Procaine (7.3·10-4 M) does not cause any further shift of s∞ in the presence of adrenaline. Atenolol (3.8·10-5 M) causes a backshift of the kinetics in the negative direction in the presence of adrenaline and procaine. The instantaneous current-voltage relationship ( {Mathematical expression}) is altered neither with adrenaline, nor with procaine or atenolol. The results exclude the possibility that the local anaesthetic side effect of many beta-adrenoceptor blocking agents may be involved in the backshift of the s-kinetics. The voltage dependence of the reciprocals of the time constants is shifted in a similar way as s∞ by the sympathomimetic or blocking drugs. Following the application of (-)-adrenaline (5.5·10-6 M) the (-)-isomere of penbutolol (1.7 and 3.5·10-6 M) is about equally effective in shifting the kinetics back as the (+)-isomere (3.5·10-5 M). In the presence of (-)-adrenaline, the (+)- and (-)-forms of penubutolol cause virtually no change of the instantaneous current-voltage relationship, {Mathematical expression}. Thus, (-)-adrenaline and (+)- and (-)-penbutolol are aiming for the s-kinetics whose voltage dependence is controlled by the electric field near the iK2-channel of the membrane and do not influence the number of the iK2-channels. These findings suggest that the sympathomimetic or blocking agents influence the s-kinetics of the pacemaker current iK2 by altering the electric field; the fully activated current-voltage relationship which is proportional to the number of the open iK2-channels is not subject to any appreciable modification. The results conclusively show that the kinetics of the pacemaker current can be controlled by beta-adrenoceptors. © 1979 Springer-Verlag.