Rate of Depression of Atrial Contractility Inducted by Citrate,Bicarbonate-Free Medium,Hydrochloric Acid,and Halothane 1

Summary

Citrate, bicarbonate-free medium, and halothane all produced rapid depressions of atrial contractility, depression occurring much more quickly than that seen by merely omitting glucose from the bathing medium. This suggests a site of action for these agents which is different from the glucose uptake step or the hexokinase step involving phosphorylation of glucose to glucoses-6-phosphate. The results are consistent with previous reports suggesting the phos-phofructokinase step as the site of action of citrate and bicarbonate-free medium and also suggests the glucose phosphate isomerase step as the site of halothane action. Hydrochloric acid produced a slow decline in contractility, similar to that seen with glucose-free medium. This can be interpreted as either a rapid effect on glucose uptake or phosphorylation or a slowly developing effect at the phosphofructokinase step. Addition of 20 mM glucose partially overcame the depression induced by citrate but had little or no effect on that produced by bicarbonate-free medium, halothane, or hydrochloric acid. This suggests that citrate depression is surmountable and probably competitive in nature while the other depressants may be of the noncompetitive type.