Function of calmodulin in postsynaptic densities. I. Presence of a calmodulin-activatable cyclic nucleotide phosphodiesterase activity

The postsynaptic density (PSD) fraction from canine cerebral cortex was found to contain an endogenous cyclic nucleotide-phosphodiesterse activity that was dependent on Mn²⁺ and/or Mg²⁺ but not on Ca²⁺. Maximal activity was obtained at 1 μM Mn²⁺. This cyclic nucleotide phosphodiesterase activity was not decreased upon removal of the calmodulin from the PSD fraction, nor was it increased by the addition of calmodulin to a postsynaptic density fraction deficient in calmodulin. The enzymatic activity could be extracted by sonication, with the soluble enzyme having properties similar to those found in the native structure. Two peaks of cyclic nucleotide phosphodiesterase activities could be obtained after S-300 Sephacryl column chromatography of this soluble fraction: fraction I (excluded peak) and fraction II (215,000 mol wt). The fraction I activity preferred cyclic AMP over cyclic GMP and was not activated by calmodulin. The fraction II activity had an approximately fourfold lower K(m) for cylcic GMP over cyclic AMP. This fraction II activity was activatable by calmodulin, which increased the V(max) and decreased the K(m) in the case of both cyclic nucleotides. We conclude that two activities are present in PSD, one activatable, and one not activatable, by calmodulin.