Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres.

Abstract

SUMMARY1. When cardiac muscle is stimulated after a rest there is a gradual increase in force development over several minutes. The origin of this 'force staircase' was investigated in experiments on sheep and dog Purkinje fibres. Particular attention was paid to the possible role of changes in the intracellular Na+ activity (aNa).2. The first line of evidence for a role for aka came from a comparison of sheep and dog Purkinje fibres generating action potentials: after a change in the stimulus rate the slow changes of both a'a and force were monophasic in sheep but biphasic in dog preparations.3. In the remaining experiments changes in aia and force in sheep preparations were measured during 4 min trains of voltage-clamp pulses at a frequency of 2-5 Hz.4. A number of these voltage-clamp experiments also indicated that changes in aka are involved. Depending on the preparation and the duration of the pulses aka rose or fell during a train -a rise in a'a was always associated with a gradual rise in force, whereas a fall in aka was usually accompanied by a gradual fall in force.The addition of tetrodotoxin (TTX) or the use of a low holding potential reduced the progressive rises of both a'a and force, whereas the inclusion of a 10 mV hyperpolarization between pulses potentiated the progressive rises of both.5. The effect of TTX on the staircase was more marked the longer the pulses during the train; this possibly indicates that the effect of aNa on the force staircase is complex and is more marked with longer pulses. 6. A rise in aia was shown not to be the only factor underlying the progressive increase in force, because in many preparations a gradual rise in force occurred in spite of no change or even a fall of aNa.7. It is concluded that an increase in aka is involved in the slow increase in force during the staircase accompanying a train of action potentials, and that other factors are also involved; various possibilities are discussed.

Mathematical models of the electrical action potential of Purkinje fibre cells

“…When the external stimulus is switched off, there is a period of quiescence before stable automaticity resumes ( figure 4c(i)). The characteristics of the simulated overdrive suppression are similar to the experimental observations by Boyett et al (1987).…”

The relationship between contraction and intracellular sodium in rat and guinea‐pig ventricular myocytes.

“…In contrast, Lederer & Sheu (1983) suggested that the progressive increase in twitch tension during the staircase in sheep Purkinje fibres was the result of the accompanying rise in aNa, because the two changes occurred over a similar time course. Evidence to support this hypothesis was obtained by Boyett et al (1987b): for example, in voltage clamped sheep Purkinje fibres they observed that tetrodotoxin decreased both the rise in a'a and the progressive increase in twitch tension during the staircase. Evidence that a'a may also be involved in the staircase in ventricular muscle was obtained by Seibel (1986): for example, he observed that tetrodotoxin decreased the progressive increase in twitch tension during the staircase in guinea-pig ventricular muscle.…”

“…In rat ventricular myocytes aia increased by 0-78 mm Hz-'. A similar rate-dependent increase in a'a (measured using Na+-sensitive microelectrodes) has been observed in guinea-pig papillary muscle (Wang et al 1988), rat atrial muscle (Ruch, Kennedy & Seifen, 1988) and sheep and dog Purkinje fibres (Cohen et al 1982;Lederer & Sheu, 1983;Ellis, 1985;Abete & Vassalle, 1987Boyet, Hart & Levi, 1987 a;Boyett et al 1987b;Lee, Im & Sonn, 1987;Bountra, Kaila & Vaughan-Jones, 1988 a, b The similarity between the results obtained in the present study and those from studies in which a'a was determined with Na+-sensitive microelectrodes suggests that the SBFI fluorescence ratio is a reasonable measure of aNa.…”

“…For example, the decrease observed in rat ventricular myocytes could have been the result of incomplete mechanical restitution (cf. Boyett et al 1987b), whereas the increase in guinea-pig ventricular myocytes could have been the result of a beat-to-beat increase in the Ca2+ current (Lee, 1987) or simply the increase in Ca2+ influx via the Ca2" current (see below).…”

Effect of repetitive activity upon intracellular pH, sodium and contraction in sheep cardiac Purkinje fibres.

“…Moreover, the presence of a clear positive force staircase at 2 and 4 Hz indicates that a positive inotropic mechanism is more than compensating for the negative inotropic influence of the intracellular acidosis. Such a positive inotropic mechanism could be the rise in aia (Lederer & Sheu, 1983;Boyett et al 1987b; see page 358 which, like the fall in pHi, increases roughly linearly with frequency (Fig. 3).…”