Dissociation between force and intracellular sodium activity with strophanthidin in isolated sheep Purkinje fibres.

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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.

Section: Methodsmentioning

confidence: 99%

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

Boyett

Hart

Levi

et al. 1987

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“…In cardiac Purkinje fibres the increase is (in part at least) the result of the rise in aia caused by the block of the Na+-K+ pump by cardiac glycosides (Wasserstrom, Schwartz & Fozzard, 1983;Eisner et al 1984; Vassalle & Lee, 1984;Boyett, Hart & Levi, 1986). However, cardiac glycosides may have another inotropic action (Noble, 1980).…”

Section: Introductionmentioning

confidence: 99%

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

Harrison

McCall

Boyett

1992

Self Cite

101

SUMMARY1. The contraction, measured optically, and the intracellular Na' activity (aNa), measured with the Na+-sensitive fluorescent dye SBFI, have been recorded simultaneously in rat and guinea-pig ventricular myocytes.2. In rat and guinea-pig ventricular myocytes at rest, a'a was 7 8 + 03 mM (n = 4) and 5-1 +0-3 mM (n = 16), respectively.3. When both rat and guinea-pig ventricular myocytes were stimulated at 1 Hz after a rest there was usually a gradual increase in twitch shortening (referred to as a 'staircase') over several minutes accompanied by an increase in a'a over a similar time course. Twitch shortening increased by 21+3 % (n = 6) and 20 + 4% (n = 16) (of steady-state twitch shortening during 1 Hz stimulation) per millimolar rise in aNa in rat and guinea-pig ventricular myocytes, respectively.4. When rat and guinea-pig ventricular myocytes were exposed to strophanthidin to block the Na+-K' pump, there were increases in twitch shortening and aia over similar time courses. Twitch shortening increased by 24 + 4 % (n = 5) and 20+3 % (n = 10) (of control twitch shortening) per millimolar rise in aNa in rat and guineapig ventricular myocytes respectively. 5. The inotropic effect of cardiac glycosides, such as strophanthidin, is widely regarded to be principally the result of the rise in aia. The similarity of the relation between twitch shortening and aia during the staircase and on application of strophanthidin suggests that the progressive increase in the strength of contraction during the staircase was also linked to the rise in aNa.6. In guinea-pig, but not rat, ventricular myocytes there was hysteresis in the relation between twitch shortening and a'a on application and wash-off of strophanthidin. This indicates that strophanthidin has another inotropic action in guinea-pig ventricular myocytes.7. A computer model of excitation-contraction coupling has been developed to simulate the staircase and the action of cardiac glycoside and to account for the relation between contraction and intracellular Na+.

“…1 Lee & Dagostino (1982), Boyett, Hart & Levi (1986), Chapman (1986) and Fabiato & Fabiato (1975). A, the effect of 0-6, 1-8 and 54 mM [Ca2+]0.…”

Section: Effect Of Na+ and Ca2+ Concentrationsmentioning

confidence: 99%

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

Šimurda

Šimurdová

Bravený

et al. 1992

SUMMARY1. The slow inward current component related to contraction (Ii,) was studied in voltage clamp experiments on canine ventricular trabeculae at 30 0C with the aims of (a) estimating its relation to electrogenic Na+-Ca2+ exchange and (b) comparing it with similar currents as reported in cardiac myocytes.2. Ii, may be recorded under conditions of augmented contractility in response to depolarizing pulses below the threshold of the classic slow inward current (presumably mediated by L-type Ca2+ channels). In responses to identical depolarizing clamp pulses the peak value of 1sic is directly related to the amplitude of contraction (Fmax). Isic peaks about 60 ms after the onset of depolarization and declines with a half-time of about 110 ms.3. The voltage threshold of Isic activation is the same as the threshold of contraction. The positive inotropic clamp preconditions shift both thresholds to more negative values of membrane voltage, i.e. below the threshold of the classic slow inward current.4. Ij, may also be recorded as a slowly decaying inwardly directed current 'tail' after depolarizing pulses. In this representation the peak value of I~j, changes with duration of the depolarizing pulses, again in parallel with Fmax. In response to pulses shorter than 100 ms both variables increase with depolarization time. If initial conditions remain constant, further prolongation of the pulse does not significantly influence either one (tail currents follow a common envelope).5. Ij, differs from classic slow inward current by: (a) its direct relation to contraction, (b) the slower decay of the current tail on repolarization, (c) slower restitution corresponding to the mechanical restitution, (d) its relative insensitivity to Ca2+-blocking agents (the decrease of I.ij is secondary to the negative inotropic effect) and (e) its disappearance after Sr2+ substitution for Ca2+.6. The manifestations ofIsic in multicellular preparations do not differ significantly from those reported in isolated myocytes (in contrast to calcium current).7.