Hysteresis in the excitability of isolated guinea pig ventricular myocytes.

Abstract

Hysteresis phenomena were demonstrated in the excitability of single, enzymatically dissociated guinea pig ventricular myocytes. Membrane potentials were recorded with patch pipettes in the whole-cell current-clamp configuration. Repetitive stimulation with depolarizing current pulses of constant cycle length and duration but varying strength led to predictable excitation (1:1) and nonexcitation (1: 0) patterns depending on current strength. However, transition between patterns depended on the direction of current strength change, and stable hysteresis loops were obtained in stimulus-response pattern versus current strength plots in 31 cells. Increase of pulse duration and decrease of stimulation rate contributed to a reduction in hysteresis loop areas. In addition, at the abrupt transitions from 1:0 to 1:1 patterns, a latency adaptation phenomenon was consistently observed. Bath application of tetrodotoxin (30 ,M) produced no change of hysteresis, whereas hysteresis was substantially decreased in cobalt (2 mM) superfusion experiments. Analysis of the changes in amplitude and shape of the subthreshold responses during the transitions from one stable pattern to the other suggested that activity led to an increase in membrane resistance, particularly in the voltage domain between resting and threshold potentials. We therefore modeled the dynamic behavior of the single cells, using an analytical solution aimed at calculating the recovery of activation latency as a function of diastolic membrane resistance. Numerical iteration of the analytical model equations closely reproduced the experimental hysteresis loops in both qualitative and quantitative ways. The effect of stimulation frequency on the model was similar to the experimental findings. The overall study suggests that the excitability pattern of guinea pig ventricular myocytes is responsible for hysteresis and bistabilities when current intensity is allowed to fluctuate around threshold levels. (Circulation Research 1991;69:1301-

Dynamics of the background outward current of single guinea pig ventricular myocytes. Ionic mechanisms of hysteresis in cardiac cells.

“…This means that threshold potential may shift to more negative values, thus increasing hysteresis of excitability. 13 It is important to point out that, in spite of the slow time course of the decrease in Q0 (Figure 3), changes in the I-V relation already are apparent after trains of only five voltage-clamp pulses. This explains why, under current-clamp conditions, a short train of action potentials may be sufficient to alter the excitability as the cell is shifted from its quiescent to its active state.…”

Hysteresis and bistability in the direct transition from 1:1 to 2:1 rhythm in periodically driven single ventricular cells

“…These transients indicate the presence of processes with long time constants. It is thus possible that including effects extending over several beats that are not presently incorporated into the ionic model ͑e.g., pumps, exchangers, time-varying ionic concentrations͒ or into the simple one-dimensional map ͑e.g., memory of excitability and APD͒ 14,36,40,41,45,46,[60][61][62] might replicate such long transients. However, there are practical experimental difficulties ͑e.g., rundown of currents͒ inherent in sorting out these slow phenomena in the single-cell preparation.…”

“…13 There is also amplitude hysteresis in the threshold for ''capture'' when an electronic pacemaker is inserted into a patient: i.e., the threshold current is slightly higher when stimulus amplitude is increased slowly from a subthreshold value than when it is decreased from a suprathreshold value. 64 While it has been suggested that the decreased threshold found when slowly decreasing stimulus amplitude during 1:1 rhythm is due to the higher coronary blood flow then present, 64 this ͕1:1↔1:0͖ hysteresis can also be seen in isolated slow-response rabbit atrium ͑where it has been termed ''excitation hysteresis''͒, 60 isolated papillary muscle, 46 single guinea-pig ventricular cells, 61 a modified version of the LR model, 62 an ''analytic'' model, 61 and a differential-difference model. 46 In sheep papillary muscle, 65 as well as in the modified version of the LR model, 62 injection of an additional stimulus ͑which is, however, subthreshold͒ during 1:1 rhythm can produce the ͕1:1→1:0͖ flip; an additional suprathreshold stimulus delivered during 1:0 rhythm can produce the ͕1:0→1:1͖ flip in the model.…”

Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes

“…We have often observed that the resting potential of the myocyte shifts slightly (within 2 mV) during control recordings, particularly when the cell is paced repetitively at a relatively short ( < 1 s) cycle length (Lorente et al, 1991). Thus, for the control runs, we always adjusted the holding potential at the onset of recording to match (within 1 mV) the value of resting potential that was measured immediately before switching to voltage clamp mode.…”