Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4-/- mice.
Agonist-induced Ca2+ entry into cells by both store-operated channels and channels activated independently of Ca2+-store depletion has been described in various cell types. The molecular structures of these channels are unknown as is, in most cases, their impact on various cellular functions. Here we describe a store-operated Ca2+ current in vascular endothelium and show that endothelial cells of mice deficient in TRP4 (also known as CCE1) lack this current. As a consequence, agonist-induced Ca2+ entry and vasorelaxation is reduced markedly, showing that TRP4 is an indispensable component of store-operated channels in native endothelial cells and that these channels directly provide an Ca2+-entry pathway essentially contributing to the regulation of blood vessel tone.
Freichel
M
M
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany.
Suh
S H
SH
Pfeifer
A
A
Schweig
U
U
Trost
C
C
Weissgerber
P
P
Biel
M
M
Philipp
S
S
Freise
D
D
Droogmans
G
G
Hofmann
F
F
Flockerzi
V
V
Nilius
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D027682:Cation Transport Proteins; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018390:Gene Targeting; D006873:Hydroquinones / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007811:Lanthanum / Q000378:metabolism; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D050052:TRPC Cation Channels; D014664:Vasodilation
D015220:Calcium Channels; D027682:Cation Transport Proteins; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel; D004533:Egtazic Acid; D007811:Lanthanum; D015544:Inositol 1,4,5-Trisphosphate; C018855:2-tert-butylhydroquinone; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000109:Acetylcholine; D002118:Calcium