Calcium-dependent 3':5'-cyclic nucleotide phosphodiesterase. Inhibition of basal activity at physiological levels of potassium ions.

A calcium-dependent cyclic nucleotide phosphodiesterase from rat cerebrum was, in the absence of activator protein, inhibited by various monovalent cations. The inhibition was rapid, readily reversible, and concentration-dependent, with 100 mM cesium, rubidium, or potassium ion inhibiting essentially all basal enzyme activity, while 100 mM sodium or lithium ions produced only moderate inhibition. The potency of the cations in inhibiting the enzyme was Cs greater than or equal to Rb greater than K greater than Na greater than or equal to Li. Potassium ions increased the apparent Km for cyclic GMP and cyclic AMP by 3- and 5-fold, respectively. At 100 mM, the monovalent cations inhibited enzyme activated by the calcium-dependent activator by only 15 to 30%, while at 55 mM no inhibition pertained. Potassium and sodium ions at 55 mM had no effect on the calcium-independent phosphodiesterase from rat cerebrum. The results indicate that at normal intracellular concentrations of potassium ions the activity of the calcium-dependent phosphodiesterase is virtually completely dependent on the presence of calcium plus activator protein.