The effects of manganese on frog heart muscle.

The effects of manganese (and some other transition elements) on the electrical and contractile properties of frog heart muscle have been investigated. The action potential duration and overshoot were dependent upon the intensity of stimulation in the presence of manganese. The cells were hyperpolarised by approximately 10 mV for a ten-fold increase in the manganese (or calcium concentration). This hyperpolarization could not completely account for the large increases in the threshold stimulus for contraction produced in manganese and high calcium solutions. The twitch contraction was rapidly and reversibly inhibited by manganese. The contracture responses produced by low-sodium solutions were greatly inhibited by manganese (I50 approximately 0.6 mM) and are largely accounted for by assuming a competitive inhibition of calcium binding by manganese. The drugs D-600 and verapamil produced little or no inhibition of the low-sodium contracture. Sodium, lithium, hydrazine and hydroxylamine were able to induce contraction in the presence of manganese following exposure to sodium-free conditions. Increasing the intracellular sodium concentration by exposure to low potassium solutions potentiated both the low-sodium contracture and the twitch contraction suggesting that intracellular sodium is important in the regulation of calcium influx. Manganese produced less inhibition of the potassium-rich contracture than of that produced by low-sodium solutions. The hyperpolarisation in manganese solutions is insufficient to account for the inhibition of the contractures produced by low-sodium or potassium-rich solutions. Contractures produced by the addition of caffeine were not inhibited by manganese. Measurements of the uptake of manganese by whole canulated ventricles indicated a large accumulation and a slow loss of part of the accumulated manganese on return to manganese-free solutions.