Calmodulin inhibits calcium influx current in vascular endothelium

Utilizing the whole‐cell configuration of the patch‐clamp technique the effect of calmodulin (CaM) on thapsigargin‐induced Ca 2+ current has been studied. Addition of several concentrations of CaM to the patch pipette induced concentration‐dependent inhibition of thapsigargin‐induced Ca 2+ current in bovine aortic endothelial cells. The effect of CaM was Ca 2+ dependent and was not observed when the intracellular Ca 2+ was buffered to 1 nM with EGTA. CaM produced two major effects on the thapsigargin‐induced Ca 2+ current. First CaM slow down activation of the current by thapsigargin from a control value of 16 ± 5 to 31 ± 6 s with 1 μM CaM in the pipette solution. The second effect of CaM was to reduce the current amplitude in a concentration‐dependent manner. The inhibition of Ca 2+ current was observed at the peak of the current and at the sustained current level. The reduction of current at the sustained level was observed 15–20 s after onset of the thapsigargin response. The half inhibitory concentration determined from these experiments was 0.1 μM. These results indicate that CaM can modulate thapsigargin‐induced Ca 2+ current in this endothelium, suggesting a possible role for CaM in the regulation of store‐operated Ca 2+ influx.