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 Ca2+ current has been studied. Addition of several concentrations of CaM to the patch pipette induced concentration-dependent inhibition of thapsigargin-induced Ca2+ current in bovine aortic endothelial cells. The effect of CaM was Ca2+ dependent and was not observed when the intracellular Ca2+ was buffered to 1 nM with EGTA. CaM produced two major effects on the thapsigargin-induced Ca2+ current. First CaM slow down activation of the current by thapsigargin from a control value of 16 +/- 5 to 31 +/- 6 s with 1 microM CaM in the pipette solution. The second effect of CaM was to reduce the current amplitude in a concentration-dependent manner. The inhibition of Ca2+ 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 microM. These results indicate that CaM can modulate thapsigargin-induced Ca2+ current in this endothelium, suggesting a possible role for CaM in the regulation of store-operated Ca2+ influx.
Vaca
L
L
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, D.F., Mexico. Ivaca@ifcsun1.ifisiol.unam.mx
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D013729:Terpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019284:Thapsigargin
D015220:Calcium Channels; D002147:Calmodulin; D004791:Enzyme Inhibitors; D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium