The effects of manganese ions on the contraction of the frog's heart

1. The effects of Mn(2+) in particular but also of Ni(2+), Co(2+), Cd(2+), verapamil and D600 on the contraction of isolated frog atrial trabeculae have been investigated. Contraction was initiated either by electrical stimulation, or by raising the [K](o) or by lowering the [Na](o).2. Mn ions like Ca ions cause a hyperpolarization of the cell membrane and a rise in the threshold for the action potential and twitch. Mn ions, particularly at low concentrations, reduce the overshoot of the ventricular action potential.3. Mn ions reduce the strength of the regularly evoked heart beats. Prolonged exposure, in beating hearts, results in a rise in resting tension and often a small recovery of the heart beat.4. In normal Ringer solution and in Ringer free of Na ions, the addition of Mn causes the tension-depolarization curve to be displaced by an amount equivalent to an 18 mV hyperpolarization of the membrane potential for a tenfold increase in the divalent cation concentration.5. Mn, Co, Ni and Cd ions all cause a marked reduction in the tension generated by exclusion of Na ions from the bathing fluid. In the presence of these divalent cations the contracture divides into an initial phasic and a later tonic contraction. This inhibition is reversed by raising the [Ca](o), while the tension developed during the initial phasic contraction varies with the [Ca](o)/[Mn](o) quotient.6. A similar tonic contracture is initiated after exposure to Na-free fluid containing a high [Mn](o) by the addition of a small concentration of Na, Li, hydrazinium or hydroxylammonium ions.7. The organic ;Ca antagonists' verapamil and D600 have little effect on the contracture induced by lowering [Na](o) even after prolonged exposure at relatively high concentrations but they do inhibit the twitch contraction and the K contractures.8. The effects of Mn on the Na-withdrawal contracture of frog heart can be interpreted in terms of an exclusively extracellular effect where Mn ions resemble Na ions in their action, and both antagonize the movement of Ca across the cell membrane.9. The experimental evidence suggests that the K contracture in frog heart is initiated by a mechanism which is, in some ways different to that underlying the Na-withdrawal contracture, and may involve two different sources of activator Ca.10. The several different effects of Mn on the frog heart probably reflects the ability of this cation to interfere with many processes involving Ca, and that there are a number of such processes involved in the results described in this work. The effects of Mn are more complex than might be generally supposed.     

The dual effect of calcium on the action potential of the frog's heart

1. Using ventricle strips of the frog's heart stimulated at the low rate of about 1 shock/min intracellular action potentials were recorded under conditions of varying calcium concentrations.2. Overshoots of action potentials were increased by about 18.3 mV as a result of a 10-fold increase, within the range of 0.1-5 mM, of the calcium concentration.3. A similar effect was obtained by strontium, but magnesium was ineffective.4. The increase of the overshoot by high calcium was associated with an increased rate of rise of the potential during the later part of its ascending phase. The initial fast upstroke remained unaltered.5. Another effect, a depression of the overshoot, developed during periods of repetitive stimulation, at the rate of 20/min, and this was followed by a gradual recovery during subsequent periods of rest.6. The depression of the overshoot increased with increasing calcium concentrations reaching values of over 40 mV.7. High concentrations of strontium and low concentrations of sodium also induced depression of the overshoot, but high magnesium was ineffective.8. A tentative hypothesis has been proposed attributing these two effects: (a) to an entry of calcium through the excitable membrane thus contributing to the ionic inward current, and (b) to a resulting accumulation of calcium in some cellular store.     

The mechanism of insulin's toxic effect on a frog's heart

Summary The author suggests that the negative effect of toxic doses of insulin on cardiac activity is possibly caused by depression of the activity of the tissue sulfhydryl groups. To obtain experimental verification of this suggestion, the author studied the action of urea on the work of the isolated frog's heart under conditions of insulin intoxication. Following the arrest of the cardiac activity caused by toxic doses of insulin, urea administration helped restore the contractile myocardial function and the ECG indices. Such an effect is evidently due to the fact that urea, which has the ability to loosen the protein molecule and liberate the tissue sulfhydryl groups, brings about the restoration of disturbed processes in the cardiac muscle.(Presented by V. N. Chernigovskii, Active Member of the AMN SSSR) Translated from Byulleten Èksperimental'noi Biologii i Meditsiny Vol. 49, No. 4, pp. 75–78, April, 1960