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

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Abstract
The ionic mechanism underlying the chronotropic effect of epinephrine on the rabbit sinoatrial (S-A) node has been studied. Epinephrine (5.5×10−6 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 (5.5×10−7 M) increased the limiting conductance for the slow inward current (i s ) by approximately 30% and the potassium current (i k ) by about 10%, keeping the kinetics ofi s andi k constant. From the holding potential of −70 mV the activation ofi s was observed on step depolarization positive to −60 or −55 mV in both control and epinephrine solution. The hyperpolarization-activated current (i h ) was also increased by about 20% at −70 mV, and its time course was slightly accelerated. Participation ofi s for the chronotropic effect of epinephrine was strongly suggested by the findings thati s was partially available positive to −60 mV and that epinephrine could not increase the slope of diastolic depolarization wheni s was blocked by D 600.