Physiological properties of atp-activated cation channels in rat
brain microvascular endothelial cells.
Janigro, Damir, T. S. Nguyen, Ellen L. Gordon, and H. Richard Winn.
Department of Neurological Surgery, Department of Environmental
Health, University of Washington, Seattle, WA 98104, phone (D.J.)
(206)-223 8716, FAX (D.J.) (206)-287 8543
APStracts 2:0439H, 1995.
Endothelial cells mediate the actions of a variety of vasoactive
substances, including adenosine 5'-triphosphate. 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 L-NA (1 mM), and L-NMA (0.1
mM). We have also investigated the electrophysiological actions of
extracellular ATP on rat brain microvascular (RBMEC) and bovine
aortic endothelial cells (BAEC) by using the patch clamp technique.
While bovine aortic endothelial cells were hyperpolarized by ATP (10
[mu]M), ATP caused the activation of a depolarizing, non-selective
cation current in brain endothelial cells. Nitric oxide production
measurements by 3H-Citrulline assay and by direct amperometric
determination also revealed that after exposure to 1-100 [mu]M ATP
RBMEC released NO. NO release from RBMEC was abolished by removal of
external Ca+2. 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
endothelium-derived relaxing factors.
Received 10 April 1995; accepted in final form 6 September 1995.
APS Manuscript Number H354-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95