The effect of heart rate on the arrhythmogenic transient inward current in isolated sheep cardiac Purkinje fibres.

Abstract

SUMMARY1. The effect of heart rate on the arrhythmogenic transient inward current ('TI) has been studied in sheep cardiac Purkinje fibres.2. Transient inward current and force (active force, tonic force and the aftercontraction) have been measured in voltage-clamped preparations. Intracellular Na+ activity (aNa) was measured simultaneously using Na+-sensitive microelectrodes. The effects of changes in voltage-clamp pulse frequency on the ITI amplitude, active force, tonic force, the after-contraction and aNa have been investigated in different bathing solutions.3. After a stepwise increase in pulse rate there was a biphasic response of ITI amplitude: a short-lasting (50 s) phase during which ITI amplitude increased followed by a decline in IT, amplitude. The second phase could be fitted by an exponential with a time constant between 102 and 184 s. The after-contraction changed in a similar biphasic manner whereas force and aNa declined monophasically; active force first declined, increased and then declined again. These changes were greater at faster rates of pulsing.4. Linear relationships between IT, amplitude, after-contraction amplitude and tonic force were observed in all experiments.5. In K+-free solution the response of the IT, was markedly changed. After an increase in pulse rate the initial increase in IT, was enhanced, whereas the subsequent decline was strongly reduced or even abolished. Potassium-free solution blocks the Na± pump, and activation of the Na+ pump by addition of Cs+ or K+ restored the phase of decay ofITI amplitude during rapid stimulation.6. A reduction of external Na+ to about 50% or elevation of external Ca2+ increased IT, but had little effect on the rate-dependent changes in the current.7. When stimulation was resumed at the basic pulse rate after a period of rapid pulsing the IT, amplitude initially continued to decline; this was followed by a slow recovery (over 10-15 min) ofITI amplitude back to its steady-state value prior to fast pulsing.8. These results are consistent with the hypothesis that changes of IT, are the

Effect of tetrodotoxin, lidocaine, and quinidine on the transient inward current of sheep Purkinje fibres

“…Similar changes could not be observed for the repolarization voltage relation of the TI in the present experiments. This is consistent with the work by Henning and Vereecke (31), and Arlock and Katzung (1) (for discussion see Noble (42)). These authors failed to show a shift of the TI reversal potential in response to a change of external Na and Ca.…”

Comparison of sodium‐calcium exchanger and transient inward currents in single cells from rabbit ventricle.

“…The effect(s) on these two currents of substitution of Ca2+ for Ba2+ or Sr2+ also emphasizes differences in their generation and/or regulation. Barium blocks the ITIS (Hennings & Vereecke, 1983). This effect is very rapid, and appears before subsequent changes in IEX ( Fig.…”

“…Barium blocks the ITIS (Hennings & Vereecke, 1983). This effect is very rapid, and appears before subsequent changes in IEX (Fig.…”