The rate of action of calcium ions on the contraction of the heart

Abstract

Calcium ions are known to facilitate the contraction of heart muscle (e.g. Niedergerke, 1956). The effect produced by a change in the external Ca concentration develops and subsides rapidly and may therefore be presumed to take place at the cell surface, yet quantitatively the rates of onset and decay appear to be too slow to be explained entirely by simple diffusion through the extracellular fluid spaces. It was of interest to obtain further evidence about the cellular localization of the Ca effect. For this purpose the rate at which the facilitating action develops or declines was compared with the rate at which labelled Ca ions are taken up by, or released from the tissue. METHODSStrips were dissected from a circular section of the wall of frog's ventricle (Rana temporaria and esculenta) (Dale, 1932). The tissue was cut into cylindrical portions of a given diameter (varying in different strips from 0 4 to 1-1 mm) following as far as possible along the main direction of the fibres within the syncytium. Strips were only employed if the variations in diameter along the length did not exceed about 10%. In one experiment a thin auricle strip was used. Auricle strips can be dissected without causing excessive damage since regions can be found where the fibres run practically parallel. However, these strips, if in good condition, beat spontaneously at a fairly high rate (about 20/min) so that they are not entirely suitable for the present investigations. Apparatus, Ringer bath and the composition of Ringer's fluid were similar to those described earlier (Niedergerke, 1956).Tracer method. Ca output was measured by a procedure similar to that used by Harris (1957) on the frog's sartorius muscle. Strips were immersed during the night in a 45Ca-labelled Ringer's solution. The tracer was then soaked out into a series of small volumes (1 or 2 ml.) of inactive Ringer's fluid. Strips were fixed with slight stretch on a holder made of thin stainless steel wire. 1 ml. samples of the 'soaking out' fluid were dried on planchettes and counted with an endwindow Geiger counter. In order to estimate the amount of labelled Ca remaining inside the tissue at the end of the 'soaking out' time, the tissue was transferred to a platinum planchette and dissolved in concentrated nitric acid so as to spread the 4"Ca evenly over the area of the planchette. The residue was incinerated at 5000 C. Before comparing the radioactivity of the ash with that of the dried portion of saline, a correction was applied to allow for the reduction due to absorption of radiation by the solid residue of the saline solution. The ash had negligible weight.

Calcium Flux and Contractility in Guinea Pig Atria

“…binding to surface sites) is necessary for the action of the ion on the contractile process. Niedergerke has inferred this from studies on frog ventricular strips (5). The similarity of half-times of the Ca 45 washout and of response of the heart to changes in calcium concentration argues against the possibility that the apparently long T1/~ for Ca 45 is primarily a function of the loss of isotope from cut edges.…”

The Interaction of Some Stimulant and Depressant Drugs on the Frog Heart

“…In the present experiments drugs which strongly stimulate hearts depressed by calcium lack, namely ouabain, paullinia tannin and oleate, were strong stimulants of hearts depressed by the two narcotics; and drugs which weakly stimulated hearts depressed by calcium lack, tannic acid and caprylate, were weaker stimulants of hearts depressed by narcotics. As hearts depressed by calcium lack lose calcium from a superficial site in the heart where calcium is required for the onward propagation of the excitatory process (Niedergerke, 1957), it may be inferred that the depressed condition of narcotized hearts is due to a similar depression in the propagation of the excitatory process (as opposed to the contractile process) and that this depression can be reversed by calcium. The observation of Berwick (1951), that concentrations of ether similar to those employed in the present experiments caused calcium loss from the frog gastrocnemius muscle, is consistent with this hypothesis.…”

“…Frog hearts depressed by perfusion with low-calcium Ringer solution lose calcium from a superficial site in the heart where calcium is required for the onward propagation of the excitatory process (Niedergerke, 1957). Hydrogen peroxide, tannic acid, paullinia tannin, sodium oleate and sodium caprylate stimulate these hearts only when there is calcium in the perfusing fluid (Broadbent, 1962b).…”

The Effect of Temperature and Frequency on the Contractile Force and Inotropic Response to Ouabain, Calcium and Some Other Drugs of the Hen Isolated Driven Auricle

“…Further, does this temperature effect on " added " calcium indicate a difference between its role in myocardial contraction and the steady state of higher contractility achieved by a bathing fluid which has a greater than normal calcium ion content and in which the temperature effect is then absent. It would appear that there is a close connection between the effect of " added " calcium and the action of digitalis (Niedergerke, 1957) but none between digitalis and calcium effects at hypothetical deeper levels which are apparently insensitive to temperature changes.…”

“…Added quantities of calcium, as calcium chloride, also showed a high dosedependent temperature effect, and, in order to determine whether the effects were similar, four-point comparisons of inotropic potency were conducted between the two drugs on the same auricle preparation at temperatures of 30 and 350 C, and at 35 and 390 C. It has previously been shown for a variety of species (for example, Niedergerke, 1957) that the inotropic effect of calcium ions is much faster than that of ouabain, and this was found to be so for the hen, maxima occurring in about one-third of the time required for ouabain. During the comparisons, whilst 1.66 and 3.33 ,ug/ml.…”