Slow inactivation of currents in cardiac Purkinje fibres

Abstract

1. When membrane currents, associated with repolarization to the holding potential, were measured in cardiac Purkinje fibres after depolarizing voltage clamp steps to the plateau level of the action potential (-20 to -10 mV), tails of inward current were observed which turned into outward current. Amplitude and duration of the tails of inward current increased when the preceding depolarization was progressively shortened. This current could only be recorded in Na-containing solution which strongly supports the view that the inactivation of sodium conductance (g(Na)) has a slow and incomplete component.2. Initial outward current (most probably chloride current (I(Cl))) during strong depolarization (beyond -20 mV) could be inactivated either by increasing the frequency of depolarizations or by applying a conditioning depolarizing prepulse.3. In Na-free solution a small, slowly decreasing inward current was recorded. This is most probably carried by calcium ions and is at least partly responsible for the negative conductance of the current-voltage relation in the voltage range -60 to -30 mV.4. If a strong conditioning depolarization (V(1)) to the inside positive potential range preceded repolarizing clamp steps to different membrane potentials (V(2)) inward current (probably calcium current (I(Ca)) could be activated in Na-free and Na-containing solutions. This current depended on the duration of V(1) as well as on the potential level of V(2). After the maximum inward current, increasing outward current occurred when the duration of V(1) was increased. This current could be explained either by an inactivation of calcium conductance (g(Ca)) with time or by a very slow activation of an additional outward current.5. The main conclusions from these experiments are that (i) slow and incomplete inactivation of g(Na) are important features for the plateau of the action potential and (ii) calcium ions carry additional charge during this phase of the action potential. Chloride conductance (g(Cl)) should be largely inactivated at a heart rate of 90/min.