Effects of calmodulin antagonists on sodium-dependent high-affinity choline uptake

The effects of calmodulin (CaM) antagonists were investigated on the sodium-dependent high-affinity choline uptake (SDHACU) as assessed by the specific binding of [3H]hemicholinium-3 ([3H]HCh-3) and high-affinity [3H]choline uptake. Potassium depolarization caused a significant 2-fold increase in the specific binding of [3H]HCh-3 in slices of rat striatum in vitro. CaM antagonists, including trifluoperazine (TFP), W-5, W-7, promethazine and haloperidol, dose-dependently inhibited potassium depolarization-stimulated [3H]HCh-3 binding with IC50s of 20, 40, 70, 30 and 48 (microM), respectively. Scatchard analysis revealed that the inhibitory effect of TFP resulted from a decrease in Bmax but no change in Kd of [3H]HCh-3 binding. Potassium depolarization of slices also stimulated high-affinity [3H]choline uptake, which was completely inhibited by 10 microM TFP. These results are discussed in relation to the regulatory mechanisms of SDHACU.