MECHANISMS OF ACTION OF BETA-ADRENERGIC AGENTS ON THE ARRHYTHMOGENIC TRANSIENT INWARD CURRENT IN RABBIT PURKINJE-FIBERS

Catecholamines increase the amplitudes of oscillatory afterpotentials (OAP) and peak magnitude of the transient inward current (Iti) responsible for OAP. The objectives of this study were to determine whether β-adrenoceptor stimulation can induce Iti, and to determine the mechanism by which β-adrenoceptor stimulation increases the magnitude of Iti. Experiments were performed using standard two electrode voltage-clamp techniques in isolated rabbit Purkinje fibers. Holding potential was either -50 or -80 mV. The Iti was elicited by repolarizing steps, following 1.5 or 3 s activating steps to potentials near 0 mV. Isoproterenol (ISO) failed to induce the Iti at concentrations from 10-8 to 10-6 m. However, ISO (10-7 m) significantly increased peak magnitude of spontaneously occurring Iti (P < 0.05), or Iti induced by acetylstrophanthidin (AS) (P < 0.05). ISO also shifted the minimum activation voltage 10 mV more negative (P < 0.05). The currentvoltage relationship demonstrated that ISO significantly increased the range of potentials over which Iti≥5 nA occurred, but did not significantly shift the voltage at which maximum peak current was observed. Effects of ISO on Iti were blocked by 10-7m propranolol or atenolol. Mn2+ (2 mm) or verapamil (2 μm) blocked the slow inward current (Isi) more than 80% before substantially decreasing peak Iti. Either agent blocked stimulation of Isi but not Iti by ISO at 10-7m. In contrast, quinacrine (20 μm), an inhibitor of Na+Ca2+ exchange, abolished stimulation of Iti by ISO while having no significant effect on Isi. Our results indicate that β-adrenoceptor stimulation cannot induce Iti in rabbit Purkinje fibers, but can enhance the Iti induced by other means, by stimulating Na+Ca2+ exchange. © 1991.