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.