Epinephrine promotes spontaneous activity in cardiac Purkinje fibers through its action on the pacemaker potassium current (iKK2). The mechanism of the acceleratory effect was studied by means of a voltage clamp technique. The results showed that the hormone speeds the deactivation of iKK2 during pacemaker activity by displacing the kinetic parameters of iKK2 toward less negative potentials. This depolarizing voltage shift is the sole explanation of the acceleratory effect since epinephrine did not alter the rectifier properties of iKK2, or the underlying inward leakage current, or the threshold for iNNa. The dose dependence of the voltage shift in the iKK2 activation curve was similar in 1.8 and 5.4 mM [Ca]o. The maximal voltage shift (usually ∼20 mV) was produced by epinephrine concentrations of > 10-6 M. The half-maximal effect was evoked by 60 nM epinephrine, nearly an order of magnitude lower than required for half-maximal effect on the secondary inward current (Carmeliet and Vereecke, 1969). The ß-blocker propranolol (10-6 M) prevented the effect of epinephrine (10-7M) but by itself gave no voltage shift. Epinephrine shifted the activation rate coefficient α8 to a greater extent than the deactivation rate coefficient ß8, and often steepened the voltage dependence of the steady-state activation curve. These deviations from simple voltage shift behavior were discussed in terms of possible mechanisms of epinephrine's action on the iKK2 channel.

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