Summary
The influence of stimulation frequency on the course of the transmembrane action potential (AP) and on the isometric tension of isolated guinea pig papillary muscles has been investigated. Special attention has been paid to the question whether the observed changes can be due to a frequency dependent increase of the extracellular concentration of Ca2+ and K+. The following results have been obtained:
1. The amplitude of the AP decreases at a stimulation frequency above 2/sec due to a diminished membrane-resting-potential (MRP) and a decrease in overshoot.
2. The duration of the AP is influenced biphasically by increasing the stimulation frequency at relatively low external calcium concentrations (1.2 and 2.4 mM). When the frequency of stimulation is increased, starting at 0.125/sec, the AP duration is prolonged at first and then shortened. At frequencies below 0.125/sec (down to 0.004/sec) the AP duration again increases.
The prolongation of the AP in the medium frequency range (between 0.125 and 0.5/sec) is minimal at a higher calcium concentration (4.8 mM).
The marked shortening of the AP duration caused by an increase in stimulation frequency above 1/sec corresponds to the frequency dependent increase in isometric tension of the papillary muscle.
3. The AP duration is shortened by 70 msec when the stimulation frequency is raised from 1/sec to 5/sec. After switching back to the lower frequency (1/sec) the disappearance of the frequency effect on the duration of the AP starts with a lower and continues with a higher speed than that on the force of contraction, the original values of both parameters being reached at the same time.
4. The extent of the frequency induced change of the AP duration is almost equal at 30%, 60% and 90% repolarisation. Consequently, the duration of the “plateau” (at 30% repolarisation) is shortened relatively more than the AP duration at 90% repolarisation.
5. The AP duration at 90% repolarisation is influenced by Ca2+ and Na+ antagonistically according to the relation [Ca2+]/[Na+]2 in the frequency range between 0.125/sec and 4.0/sec. In contrast, the extent of the shortening of the “relative duration of the plateau” depends on the external sodium concentration ([Na+] e ).
The lesser shortening of the “relative duration of the plateau” at a decreased [Na+] e (70 mM instead of 140 mM) corresponds to a decreased positive inotropic frequency effect.
6. The MRP is decreased by 8 mV when the stimulation frequency is increased from 1/sec to 5/sec. Considering the relation between MRP and [K+] e at a stimulation frequency of 1/sec a frequency induced increase of [K+] e from 5.9 mM to 8–9 mM can be assumed. Such an increase in [K+] e , however, only causes a shortening of the AP duration by 6 msec. Concomitantly, the relative duration of the plateau is prolonged.
7. The shortening of the AP duration of about 70 msec due to an increase of the stimulation frequency from 1/sec to 5/sec equals—as does the augmentation of the contractile force of the muscle—the effect of a two—or threefold elevation of the external calcium concentration.
Similarly the lengthening of the AP duration by an increase in stimulation frequency from 0.125 to 0.5/sec at a relatively low external calcium concentration (1.2 mM) equals the effect of raising the [Ca2+] e .
8. The results lead to the conclusion that the influence of the frequency of stimulation on the duration of the action potential is caused mainly by an increase of the calcium concentration at the outside of the cell membrane while the decrease of the membrane-resting-potential as well as of the overshoot may be the result of an extracellular accumulation of K+.
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Die vorläufige Mitteilung eines Teils der Ergebnisse erfolgte durch einen Vortrag vor der Deutschen Pharmakologischen Gesellschaft im Frühjahr 1967 (Reiter, M., u. F. J. Stickel, 1967).
Die Untersuchungen wurden mit Unterstützung durch die Deutsche Forschungsgemeinschaft ausgeführt.
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Reiter, M., Stickel, F.J. Der Einfluß der Kontraktionsfrequenz auf das Aktionspotential des Meerschweinchen-Papillarmuskels. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 260, 342–365 (1968). https://doi.org/10.1007/BF00537639
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DOI: https://doi.org/10.1007/BF00537639