The relation between the current underlying pacemaker activity and beta-adrenoceptors in cardiac Purkinje fibres: A study using adrenaline, procaine, atenolol and penbutolol

Summary

The pacemaker current — i _K2 — 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 ($\overline {i_{K2} }$) 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, $\overline {i_{K2} }$. Thus, (−)-adrenaline and (+)- and (−)-penbutolol are aiming for the s-kinetics whose voltage dependence is controlled by the electric field near the i _K2-channel of the membrane and do not influence the number of the i _K2-channels. These findings suggest that the sympathomimetic or blocking agents influence the s-kinetics of the pacemaker current i _K2 by altering the electric field; the fully activated current-voltage relationship which is proportional to the number of the open i _K2-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.