TRP PROTEINS FORM STORE-OPERATED CATION CHANNELS IN HUMAN VASCULAR ENDOTHELIAL-CELLS

Members of the Trp protein family have been suggested as the structura l basis of store-operated cation conductances. With this study, we pro vide evidence for the expression of three isoforms of Trp (hTrp1, 3 an d 4) in human umbilical vein endothelial cells (HUVEC), The role of Tr p proteins in store regulation of endothelial membrane conductances wa s tested by expression of an N-terminal fragment of hTrp3 (N-TRP) whic h exerts a dominant negative effect on Trp channel function presumably due to suppression of channel assembly. Depletion of intracellular Ca 2+ stores with IP3 (100 mu M) or thapsigargin (100 nM) induced a subst antial cation conductance in sham-transfected HUVEC as well as in HUVE C transfected with hTrp3, In contrast, HUVEC transfected with N-TRP fa iled to exhibit store-operated currents. Our results suggest the invol vement of Trp related proteins in the store-operated cation conductanc e of human vascular endothelial cells. (C) 1998 Federation of European Biochemical Societies.