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 approximately 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 beta-blocker propranolol (10(-6) M) prevented the effect of epinephrine (10(-7)M) but by itself gave no voltage shift. Epinephrine shifted the activation rate coefficient alpha(8) to a greater extent than the deactivation rate coefficient beta(8), 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.
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D006329:Heart Conduction System / Q000378:metabolism*; D066298:In Vitro Techniques; D011188:Potassium / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000378:metabolism*; D013268:Stimulation, Chemical
D011433:Propranolol; D011188:Potassium; D004837:Epinephrine