Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres.

Abstract

SUMMARY1. Voltage clamp experiments studied the ionic basis of the strophanthidininduced transient inward current (TI) in cardiac Purkinje fibres.2. The reversal potential of TI (Erev) was determined in the presence of various bathing solutions. Erev averaged -5 mV in the standard modified Tyrode solution (Kass, Lederer, Tsien & Weingart, 1978). Erev was displaced toward more negative potentials when the external Na concentration (Na0) was reduced by replacement of NaCl with Tris Cl, choline Cl or sucrose.3. 'A sudden reduction of Nao evoked a temporary increase in TI, followed after a few minutes by a sustained diminution. The initial increase was closely paralleled by an enhanced aftercontraction and could be explained by an indirect effect of Nao on internal Ca. The subsequent fall in TI amplitude could be accounted for by the reduced driving force, E -Erev. (1-8 mM).5. These results are consistent with an increase in membrane permeability to Na and perhaps K.6. TI was not directly affected by TTX, which blocks excitatory Na channels, or by Cs, which inhibits inwardly rectifying K channels. TI may be distinguished from the slow inward current by its kinetic, pharmacological and ionic properties.7. TI might be carried by a pre-existing ionic pathway such as the 'leak' channel which provides inward current underlying normal pace-maker depolarization. Another possibility is that TI reflects Ca extrusion by an electrogenic Ca-Na exchange.

2APB- and JTV519(K201)-sensitive micro Ca2+ waves in arrhythmogenic Purkinje cells that survive in infarcted canine heart

“…Subsequently, spontaneous contractions, spontaneous oscillations in both current and potential, were described in both multicellular and myocyte preparations. 33 - 35 The amplitude of spontaneous Ca 2+ oscillations depends on the level of intracellular Ca 2+ much like the triggered oscillations in Ca i that have been shown to be concomitant with delayed afterdepolarizations. 36 -38 Thus, spontaneous Ca 2+ oscillations are not due to transmembrane potential changes but, given the correct initiating conditions, cause traveling Ca 2+ waves, depolarizations, and nondriven action potentials.…”

Influence of lorcainide on microsomal Na+, K+‐ATPase in guinea‐pig isolated heart preparations

“…The inhibition of the Na+, K+-ATPase by cardiotonic steroids is believed to be the mechanism underlying digitalis toxicity (Smith et al, 1984). This is also associated with the production of the transient inward current (Kass et al, 1978). Since this current is probably carried by a pathway that is permeable to both sodium and potassium ions, and its inhibitors are known to exert important effects on digitalis-induced arrhythmias (Kass et al, 1978), a mechanism could be envisaged whereby lorcainide may indirectly impede it by its direct actions on the Na+, K+-ATPase activity.…”

Two differential mechanisms of automaticity in diseased human atrial fibers.

“…An increase in [Ca2 +]; seems to lead to an oscillatory release of Ca2 + from the sarcoplasmic reticulum (SR, ORCHARD et al, 1983), which then increases the membrane conductance for cations such as Na+ and K+ and elicits a transient inward current (KAss et a!., 1978). The current is responsible for delayed afterdepolarizations and triggered activity (HOFFMAN and ROSEN, 1981).…”

“…Therefore proportional shortening of the CL of automaticity encountered on the progressive dilatation of right atrium may be, at least in part, a reflection of the gradual increase in the intracellular Cat + concentration. It seems that, as the atrial size is enlarged, the slow diastolic depolarizations mediated by the pacemaker current ('Ca) are altered to the transient depolarizations produced by the transient inward current (KASS et al, 1978) or by the electrogenic Na-Ca exchange (Lapp and PoTT, 1988). On the other hand, in the case of digitalis-treated patients (group 2), the CL of automaticity should have been determined already by the transient depolarization of short CLs.…”