Inhibition by K⁺ of uptake₂ of³H-(±)-isoprenaline in the perfused rat heart

Summary

The kinetics of the inhibitory effect of extracellular K⁺ on uptake₂ of³H-(±)-isoprenaline were determined in isolated hearts obtained from reserpine-pretreated rats; catechol-O-methyl transferase was inhibited.

• 1. Initial rates of uptake₂ of a very low concentration of³H-(±)-isoprenaline (10 nmol/l) were determined in the presence of various extracellular concentrations of K⁺ (2.7 to 60 mmol/l). The inhibitory effect of K⁺ was concentration-dependent with an IC₅₀ of about 20 mmol/l. — In these experiments KCl was added to the perfusion solution, and some hypertonicity resulted. In some experiments NaCl was added to a solution containing 5 mmol/l K⁺ to result in the same degree of hypertonicity as that obtained for 60 mmol/l K⁺; hypertonicity increased the initial rate of uptake₂ of³H-(±)-isoprenaline. Thus, the inhibitory effect of K⁺ had been slightly underestimated.

• 2. In subsequent experiments the increase of the concentration of K⁺ in the perfusion fluid to 30 mmol/l was compensated for by a corresponding reduction of Na⁺. Initial rates of uptake₂ of 10 nmol/l³H-(±)-isoprenaline were determined in the absence and presence of various concentrations of unlabelled (±)-isoprenaline. At 30 mmol/l K⁺ the IC₅₀ (=K _m for uptake₂) did not significantly differ from that determined in an earlier study of 2.7 mmol/l K⁺ (Grohmann and Trendelenburg 1984). Finally, theV _max for uptake₂ of³H-(±)-isoprenaline was determined at either 2.7 or 30 mmol/l K⁺. At 30 mmol/l K⁺ theV _max was only about 1/4 of that observed at 2.7 mmol/l K⁺.

• 3. Extracellular K⁺ inhibits uptake₂ of³H-(±)-isoprenaline primarily by a reduction ofV _max.