Inward current related to contraction in guinea‐pig ventricular myocytes.

Abstract

SUMMARY1. A component of inward current has been identified in isolated guinea-pig ventricular cells that is closely correlated with the contraction of the cell and not with the rapidly activated calcium current. This is a delayed current most clearly seen as a current 'tail' after 50-200 ms depolarizing pulses. At 22°C the delayed current has a maximum amplitude of -05 nA at -40 mV (consistently 10-20 %O of the peak amplitude of the calcium current) and decays with a half time of -150 ms.2. Paired-pulse protocols show that at pulse intervals (300-400 ms) at which the calcium current is nearly fully reprimed, the delayed component is very small. It recovers over a time course of several seconds, as does the contraction. Adrenaline speeds the decay of the delayed current (-50°/) and similarly accelerates cell relaxation. Adrenaline also shortens the recovery time of both the contraction and the delayed current. 3. During long trains of repetitive pulses, the delayed current amplitude follows that of the contraction 'staircase'. The half-time of the decay of the current 'tail' also matches that of contraction and suggests that both may reflect the time course of the underlying intracellular calcium transient.4. The half-time of decay of the delayed current is only moderately voltage dependent over the potential range -80 to 0 mV. The amplitude of the delayed current normally reaches a minimum around -20 mV and increases at more negative potentials.5. The voltage dependence and kinetics of decay of the current show that it should flow and decay largely during the action potential plateau and repolarization rather than during diastole.6. Diffusion of high concentrations of EGTA into cells abolishes the delayed current and cell contraction. Under these conditions the fast calcium current is increased and its inactivation delayed.7. When calcium is replaced by strontium, the delayed current amplitude is greatly reduced even though the contraction is larger and slower.8. The results are consistent with the hypothesis that the delayed inward current is activated by the intracellular calcium transient. It may be carried by the sodium-calcium exchange process and/or by calcium-activated non-specific channels (especiallv when internal calcium is elevated by reduction of external sodium).9. In the presence of 1 ,tM-ryanodine, the calcium current is greatly reduced, whereas the delayed current is not significantly altered.

A contraction‐related component of slow inward current in dog ventricular muscle and its relation to Na(+)‐Ca2+ exchange.

“…The delayed inwardly directed tail currents similar to the current investigated in this work have so far been identified in isolated cells of various species including rat (Mitchell et al 1984), guinea-pig (Fedida et al 1987;Beuckelmann & Wier, 1988), frog (Hume, 1987;Campbell et al 1988) and rabbit (Giles & Shimoni, 1989b). The relation between delayed tail current and contraction was studied by Fedida et al (1987) in guinea-pig ventricular myocytes.…”

“…The relation between delayed tail current and contraction was studied by Fedida et al (1987) in guinea-pig ventricular myocytes. The comparison between characteristic properties of this current and Ij,1 indicates an essential identity for both.…”

“…The relation to contraction of the slow tail currents in isolated myocytes was first studied in detail by Fedida et al (1987), who clearly demonstrated close positive correlation between both quantities. Most authors suggest that these currents may 50 CONTRACTION-RELATED SLOW INWARD CURRENT be accounted for by the electrogenic Na+-Ca2+ exchange process.…”

“…These currents were recorded in response to the offset of depolarizing pulses as slow tail currents, clearly different from ICa deactivation (Mitchell, Powell, Terrar & Twist, 1984;Fedida, Noble, Shimoni & Spindler, 1987;Hume, 1987;Campbell, Giles, Robinson & Shibata, 1988;Giles & Shimoni, 1989a, b;Egan, Noble, Noble, Powell, Spindler & Twist, 1989), or in response to the onset of depolarizing pulses (Lee, Lee, Noble & Spindler, 1983;Brown, Noble, Noble & Taupignon, 1986;Boyett, Kirby & Orchard, 1988).…”

The giant cardiac membrane patch method: stimulation of outward Na(+)‐Ca2+ exchange current by MgATP.

“…The Na+-Ca2+ exchange process in heart has been extensively studied in sarcolemmal vesicles (for review, see Reeves & Philipson, 1989), as well as in intact tissue (Hilgemann, 1986) and in isolated cardiac myocytes using whole-cell voltage clamp (Kimura, Noma & Irisawa, 1986;Kimura, Miyamae & Noma, 1987;Fedida, Noble & Shimoni, 1987;Campbell, Giles & Robinson, 1988;Egan, Noble & Noble, 1989;Earm, Ho & So, 1989) and optical methods (Barcenas-Ruiz, Beuckelmann & Wier, 1987;Crespo, Grantham & Cannell, 1990). Many properties of the exchanger are consistent among these different experimental approaches; for example, rates of sodium-dependent calcium efflux during repolarization and the accompanying action potential changes were well explained by the current densities of the inward exchange current found in myocytes (Hilgemann & Noble, 1987).…”