Slow inward current and its role mediating the chronotropic effect of epinephrine in the rabbit sinoatrial node

The ionic mechanism underlying the chronotropic effect of epinephrine on the rabbit sinoatrial (S-A) node has been studied. Epinephrine (5.5 X 10(-6) M) increased the spontaneous rate from 206 +/- 25 min-1 to 242 +/- 39 min-1. The effect of epinephrine was reproducible on repetitive applications. Voltage clamp experiments using the two microelectrode technique revealed the following changes in the membrane current: epinephrine (5.5 X 10(-7) M) increased the limiting conductance for the slow inward current (is) by approximately 30% and the potassium current (ik) by about 10%, keeping the kinetics of is and ik constant. From the holding potential of -70 mV the activation of is was observed on step depolarization positive to -60 or -55 mV in both control and epinephrine solution. The hyperpolarization-activated current (ih) was also increased by about 20% at -70 mV, and its time course was slightly accelerated. Participation of is for the chronotropic effect of epinephrine was strongly suggested by the findings that is was partially available positive to -60 mV and that epinephrine could not increase the slope of diastolic depolarization when is was blocked by D 600.