Intersarcomere dynamics of single muscle fibers during fixed-end tetani.

Abstract

Epinephrine promotes spontaneous activity in cardiac Purkinje fibers through its action on the pacemaker potassium current (iK_K2). 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 iK_K2 during pacemaker activity by displacing the kinetic parameters of iK_K2 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 iK_K2, or the underlying inward leakage current, or the threshold for iN_Na. The dose dependence of the voltage shift in the iK_K2 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 iK_K2 channel.