The Effects of Substrates on Rat Atria Depressed with Bicarbonate-Free Medium,Citrate,or Low Calcium 1

Abstract

Summary

Atria, incubated in bicarbonate-free medium containing 5.5 mM glucose at pH 7.4, demonstrated a progressive decline in contractility not seen in bicarbonate-containing normal medium. Addition of 5 ml pyruvate, lactate, or acetate to atria depressed by bicarbonate-free medium produced a marked increase in contractility. Such an effect was not seen by addition of glucose (30 mM) or fructose (20 mM) indicating a block in the Embden-Meyerhof pathway produced by the bicarbonate-free medium at some point between fructose and pyruvate and most probably at the phos-phofructokinase step.

Addition of citrate to atria incubated in the normal bicarbonate-containing medium produced dose-dependent decreases in contractility. The effects of substrates on citrate-depressed atria were in some respects similar to their effects on atria depressed by bicarbonate-free medium. Pyruvate (5 mM) and lactic acid (5 mM) increased the force of contraction of citrate-depressed atria whereas fructose (30 mM) was without effect. These results are consistent with an inhibitory effect of citrate at some point in the Embden-Meyerhof pathway such as the phosphofructokinase step. Addition of acetate (5 mM) to citrate-depressed atria produced little, if any, effect. Additional glucose (20 mM) produced a marked positive inotropic effect in citrate-depressed atria, This is not in accord with a citrate-induced block of phos-phofructokinase unless one postulates an effect of glucose on contractility which is not dependent on its metabolism via the phos-phofructokinase step. The mechanism of the depressant action of citrate cannot be solely attributed to a lowering of ionized medium calcium by chelation with citrate since the action of substrates on atria depressed by low calcium was quite different from their action on citrate-depressed atria. Pyruvate and lactic acid, which produced marked increases in contractility of citrate-depressed atria, were without effect on atria depressed by low calcium. Addition of glucose had less effect on atrial contraction when added to the low-calcium medium than when added to the citrate medium. Indeed, the marked positive inotropic action of 20 mM additional glucose seen in normal or citrate-depressed atria was virtually abolished in atria depressed by removal of 3/4 of the calcium from the medium.