Mechanisms of excitation-contraction coupling studied using the principle of transient perturbation

Abstract

We have studied the responses to a brief interruption of a train of steady state beats, namely: (1) a single prolonged depolarisation within the train; (2) a single short interval within the train; (3) a single long interval within the train. These responses are predicted by a two compartment model of intracellular calcium handling. They are characterised by the following phenomena. (1) Prolongation of one depolarisation/action potential in the steady state train causes potentiation of the following beat. We postulate on the basis of the published evidence that this may be due to "reversed" sodium/calcium exchange during late systole leading to extra calcium entry during the prolonged depolarisation. (2) Postextrasystole potentiation is postulated to share this mechanism when a depolarisation (extrasystole) is introduced immediately after one of the steady state depolarisations (single short interval). The postextrasystolic beat is then potentiated. (3) A single short interval during the steady state train also leads to attenuation of contractile force on the beat immediately after the short interval, that is, the extrasystole. Mechanical restitution is the term applied to the recovery of this force with increasing interval. This consists of two phases. The initial rapid phase is ryanodine and caffeine insensitive, indicating possible independence of sarcoplasmic reticular function. We postulate that a "membrane compartment" of internal calcium may be responsible. The second, slower, phase of mechanical restitution is ryanodine and caffeine sensitive, indicating that it is likely to be a property of the sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation of the contraction following a prolonged depolarization in isolated ferret myocardium

“…We have previously found (Arlock & Wohlfart 1990, Noble et al . 1993), and again demonstrate in the left hand panel of Figure 3, that the first 100–120 ms of test clamp 1 is neutral for net calcium entry as evaluated from the contraction.…”

“…1983, Arlock & Wohlfart 1990, Arlock et al . 1991a, Noble et al . 1993) we assume that calcium entry during a particular depolarization is taken into an `uptake' compartment of the internal store and transferred with diastolic time during the next interval to a `release compartment'.…”

“…In an attempt to develop a hypothesis for the mechanism of `post long clamp potentiation' (Arlock & Wohlfart 1990, Noble et al . 1993) we previously sought a source of calcium entry during depolarization 1 that would be manifest as increased calcium release during depolarization 2.…”

“…The sodium‐calcium exchange current is postulated to go from a forward (calcium extrusion) mode to a reversed (calcium influx) mode after about l00 ms of systolic depolarization – the `dead time', Figure 3 (Drake‐Holland et al . 1983, Noble et al . 1993).…”

Mechanical Restitution in Atrial Muscle from Human and Rat Hearts: Effects of Agents that Modify Sarcoplasmic Reticulum Function

“…view see Seed & Walker 1988) or to recovery of the sarcoplasmic reticulum Caz+release channels from inactivation (Wier & Yue 1986). The second phase of potentiation represents the loading of the sarcoplasmic reticulum with Ca" although it is not clear where this extra Ca2+ comes from (for discussion see Noble et al 1993). The third phase of force decline reflects loss of Ca2+ from the cell (Wendt-Gallitelli 1986;Schouten 1990).…”