Physiological properties of ATP-activated cation channels in rat brain microvascular endothelial cells.
Endothelial cells mediate the actions of a variety of vasoactive substances, including ATP. ATP vasodilatatory actions have been shown to depend on a calcium-dependent release of endothelium-derived relaxing factor(s) (EDRF). ATP induced a vasodilatation of pial penetrating microvessels when applied intraluminally; these relaxations were mediated by the endothelium and followed release of nitric oxide (NO), since they were sensitive to blockade of NO-synthesizing enzymes by NG-nitro-L-arginine (1 mM) and NG-mono-methyl-L-arginine (0.1 mM). We have also investigated the electrophysiological actions of extracellular ATP on rat brain microvascular (RBMEC) and bovine aortic endothelial cells (BAEC) using the patch-clamp technique. While BAEC were hyperpolarized by ATP (10 microM), ATP caused the activation of a depolarizing nonselective cation current in brain endothelial cells. NO production measurements by [3H]citrulline assay and by direct amperometric determination also revealed that after exposure to 1-100 microM ATP, RBMEC released NO. NO release from RBMEC was abolished by removal of external calcium. We conclude that, in the brain, ATP exerts its vasoactive roles by altering the electrophysiological properties of endothelial cells by acting on receptor-operated ion channels, thus providing a mechanism for calcium entry and subsequent release of EDRF.
Janigro
D
D
Department of Neurological Surgery, University of Washington, Seattle 98104, USA.
Nguyen
T S
TS
Gordon
E L
EL
Winn
H R
HR
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002412:Cations / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D002412:Cations; D007473:Ion Channels; D009569:Nitric Oxide; D000001:Calcimycin; D000255:Adenosine Triphosphate