Annexin II modulates volume-activated chloride currents in vascular endothelial cells.
The membrane-associated, microfilament-binding protein annexin II is abundantly expressed in endothelial cells from calf pulmonary artery (CPAE cells). We have analyzed its role in the regulation of volume-activated chloride currents (ICl, vol) by loading the cells via the patch pipette with a peptide comprising the N-terminal 14 residues of annexin II. This sequence harbors the binding site for the intracellular annexin II ligand, p11, and the peptide interferes with the annexin II-p11 complex formation. Loading of a CPAE cell with this peptide caused a gradual decrease in the amplitude of ICl, vol during repetitive stimulations with a 28% hypotonic extracellular solution. This run down of the current was virtually absent in untreated cells and in cells that were loaded with a mutated 14-amino acid peptide, which has a single amino acid replacement known to result in a more than 1000 times reduced affinity for binding to p11. We conclude that annexin II-p11 complex formation is either directly or indirectly involved in the activation of ICl, vol in endothelial cells.
Nilius
B
B
Laboratorium voor Fysiologie, KU Leuven, B-3000 Leuven, Belgium. bernd.nilius@med.kuleuven.ac.be
Gerke
V
V
Prenen
J
J
Szücs
G
G
Heinke
S
S
Weber
K
K
Droogmans
G
G
D000818:Animals; D017306:Annexin A2 / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002417:Cattle; D002460:Cell Line; D048429:Cell Size; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D009418:S100 Proteins; D014882:Water-Electrolyte Balance; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D002118:Calcium; D018118:Chloride Channels; D002712:Chlorides; D010446:Peptide Fragments; D010455:Peptides; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10