The arrhythmogenic transient inward current iTI and related contraction in isolated guinea‐pig ventricular myocytes.

Abstract

SUMMARY1. The arrhythmogenic transient inward current, iTI, and contractions were recorded in isolated guinea-pig ventricular myocytes, after exposure to strophanthidin or low external K+ (0-5 mM), using a single-microelectrode voltage-clamp technique and an optical measure of contraction.2. The inward current, iTI, and after-contraction occurred on repolarization after a depolarizing pre-pulse. Longer pre-pulses to more positive potentials increased the size and reduced the latency of iTI* Oscillatory currents and contractions also occurred during pulses to positive potentials.3. The voltage dependence of iTI was studied by repolarizing to different potentials after a constant depolarizing pulse. Inward currents preceded after-contractions at all potentials. The iTI was maximal at about -50 mV, diminishing in magnitude at more negative and positive potentials. It remained inward at potentials up to +47 mV. The contraction exhibited a similar voltage dependence. The currentvoltage relation varied in the same cell with longer exposure to glycosides. Thus, the voltage dependence of iTI reflected not only that of an underlying ionic mechanism but also the effects of potential on intracellular Ca2" oscillations which trigger iTI' 4. Uniformity of internal Ca2+ transients was achieved by clamping to different potentials at the peak of an inward current. The iTI remained inward at positive potentials. An inward tail current, seen on repolarizing during iTI at the end of a depolarizing pre-pulse, progressively increased at negative potentials. This voltage dependence may be close to that of the Ca2+-activated inward current responsible for 1TI 5. Replacement of Na+ by Li+ initially increased the magnitude of iTI, but further exposure abolished the inward current, while the after-contractions continued to increase. The potential dependence of iTI was not affected by exposure to zero Na+. Replacement of Ca2+ by Sr2+ also abolished iTI and the after-contraction, but the main effect was to slow their occurrence.6. The voltage dependence of the Ca2+-activated inward current in guinea-pig ventricular myocytes leads us to favour electrogenic Na-Ca exchange current as a major component of iTI, under our experimental conditions.

An Antagonist of cADP-ribose Inhibits Arrhythmogenic Oscillations of Intracellular Ca2+ In Heart Cells

“…2. These transient inward currents are likely to be secondary to spontaneous Ca 2ϩ release from an overloaded SR and are thought to be carried predominantly by sarcolemmal Na ϩ /Ca 2ϩ exchange operating in the Ca 2ϩ extrusion mode (20,21). In this cell, subsequent infusion of 20 M 8-amino-cADPR (in the continued presence of isoproterenol) was associated with complete suppression of transient inward currents within 5 min (Fig.…”

Acceleration of Ca2+ Waves in Monocrotaline-Induced Right Ventricular Hypertrophy in the Rat

“…The amplitude of DADs linearly correlated with the velocity and amplitude of Ca 2+ waves, probably through the NCX current (Figure 4), 16,17 suggesting that, in the present study, acceleration of Ca 2+ waves enhanced arrhythmogenesis in both the Ctr-and MCT-rats. The steeper slope of the relationship in the MCT-rats may be due to the increased expression of the NCX.…”

Antiarrhythmic effects of BN‐063, a newly synthesized adenosine A1 agonist, on myocardial ischaemia in rats

“…There was a highly significant correlation between adenosine and the stimulation of catecholamines in in vitro studies. Adenosine not only antagonizes isoprenaline-induced increases in ICa but also inhibits catecholamine induced ITi and triggered activity (Belardinelli & Isenberg, 1983;Fedida et al, 1987). It is likely that adenosine antagonism of catecholamine stimulated increases in ICa resulted from effects on intracellular cyclic AMP levels (Lerman & Belardinelli, 1990).…”

“…High local noradrenaline (NA) levels may be achieved by either local nonexocytotic release (Abrahamsson et al, 1985;Schomig et al, 1987) or exocytotic NA release due to activa-_ tion of cardiac sympathetic nerves (Lombardi et al, 1983;Zaza & Schwartz, 1985). However, catecholamine-induced increases in the inward calcium current (ICa) and transient inward current (ITi) (Belardinelli & Isenberg, 1983;Fedida et al, 1987) which have been implicated in the genesis of afterdepolarization and triggered activity, are potentially arrhythmogenic in the ischaemic heart. Myocardial ischaemia facilitates adenosine release which may reduce the consequences of impaired myocardial tissue perfusion.…”