Epinephrine and the pacemaking mechanism at plateau potentials in sheep cardiac Purkinje fibers.

1. In 1.35 mM [K+]0, sheep cardiac Purkinje fibers depolarized to about -40 mV. Whereas some fibers oscillated spontaneously at plateau potentials, others could be made to oscillate when polarized by intracellular currents. Pacemaker activity at plateau potentials (-50 to 0 mV) was distinct from that caused by the iK2 pacemaker at more negative potentials (-60 to -100 mV). 2. Epinephrine induced spontaneously occurring action potentials and increased pacemaker activity in depolarized Purkinje fibers. The ED50 for the positive chronotropic effect of epinephrine was about 5 x 10(-7) M. This concentration is similar to that reported for the effect of epinephrine on plateau amplitude (Carmeliet and Vereecke, 1969) and the slow inward current (isi, Reuter, 1974). 3. In voltage clamp experiments, epinephrine, increased the magnitude of isi and of an outward plateau current, ixi. It is concluded that epinephrine effects pacemaking at plateau potentials by increasing isi and without shifting the voltage dependence of these currents. The onset of pacemaker activity by epinephrine was preceded by membrane depolarization that results from an inward shift of the steady-state current-voltage relation. This current may flow through isi channels that are activated but not completely inactivated.