Effects of Epinephrine on the Pacemaker Potassium Current of Cardiac Purkinje Fibers

Epinephrine promotes spontaneous activity in cardiac Purkinje fibers through its action on the pacemaker potassium current (i_KK2). 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 i_KK2 during pacemaker activity by displacing the kinetic parameters of i_KK2 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 i_KK2, or the underlying inward leakage current, or the threshold for i_NNa. The dose dependence of the voltage shift in the i_KK2 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 i_KK2 channel.