MV Levels Research Articles

Effects of manganese, glucose and isoprenaline on the action potential of anoxic ventricular muscle.

Anoxia has previously been shown to depress the action potential of guinea pig ventricular muscle. It seemed possible that the anoxia-induced decreases in action potential duration and overshoot were related to a reduction in the slow inward current. The following indirect evidence was obtained in support of this view: 1. Anoxic muscle incubated in 50 mM glucose medium has a normal action potential duration and overshoot. In 5 mM glucose medium the action potential duration was severely reduced with only a small decline in overshoot. In the absence of glucose the action potential duration was further reduced and the amplitude was depressed by about 35 mV. Reincubation in 50 mM glucose medium quickly restored both duration and overshoot. 2. In 50 mM glucose medium, 20 mM manganese chloride (Mn++) reduced the action potential duration and overshoot. Both parameters were restored after washing with Mn++-free medium. 3. Changes in action potential duration at the 0 mV and +20 mV levels were correlated with changes in peak tension and rate of rise of tension. 4. Isoprenaline restored the reduced action potential duration of anoxic muscle incubated in 5 mM glucose medium: This effect was blocked by Mn++.

Studies of the excitation-contraction mechanism in the skeletal muscle and the myocardium.

The quantitative relationship between the active state duration and the duration of the action potential was investigated by recording both these parameters under identical conditions in the same isolated fibre (semitendinosus muscle of the frog), the mechanical measurements being confined to 2.1 μ sarcomere spacing. A graded widening of the repolarization phase of the spike potential, without any change of the rising phase and the total amplitude of the action potential, was achieved by adding zinc (2.5–10×10−6 M) to the extracellular medium. The active state duration and the degree to which it was changed by a widening of the action potential varied substantially from fibre to fibre. For each individual fibre, however, an almost linear relationship existed between the action potential duration (measured at the 0 and −25 mV levels) and the duration of the active state determined at 50% of maximal activity. In view of the fact that the mechanical threshold was unaffected under the experimental conditions used, this finding provides strong support for the idea that the duration of the action potential, although only 1/10 the width of the mechanical response, is a determinant of the time course of the active state. This observation is consistent with the hypothesis that the action potential determines the release of an activator into the myofibrillar space, the removal of which is a relatively slow process. By contrast to the situation in the skeletal muscle the maximal intensity of the active state in the myocardium is a variable. There is furthermore no clear plateau of the active state curve of the cardiac muscle. These facts would seem to indicate that, unlike conditions in the skeletal muscle cell, the contractile system of the myocardium does not attain mechanical saturation during a period of activity.