Affiliation:
1. From the Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
Abstract
Hemodynamic shear stress elicits a rise in endothelial [Ca
2+
]
i
, which may serve as a key second messenger to regulate many flow-associated physiological and biochemical processes. In the present study, we used Mn
2+
quenching of fluorescent dye Fluo3 as an assay to investigate the Ca
2+
influx of rat aortic endothelial cells in response to flow. We found that the Ca
2+
signaling in response to flow could be greatly influenced by the status of intracellular Ca
2+
stores. Depletion of intracellular Ca
2+
stores by thapsigargin (4 μmol/L) or cyclopiazonic acid (10 μmol/L) drastically sensitized the Ca
2+
influx in response to flow. Ca
2+
-mobilizing agonist bradykinin (100 nmol/L) or ATP (100 μmol/L) had similar sensitizing effect. The effect of bradykinin or ATP was blocked by
Xestospongin C
and U73122, suggesting that the sensitization was related to the IP
3
-mediated store depletion. On the other hand, the Mn
2+
quenching in response to flow was greatly reduced by ochratoxin A (100 nmol/L), an agent that could increase the filling state of intracellular Ca
2+
stores. In addition, we found that depletion-sensitized Ca
2+
influx in response to flow was mediated by a PKG-inhibitable cation channel and that the influx was affected by membrane potential and K
+
channel activity. In conclusion, the present study argues for a critical role of intracellular Ca
2+
status in determining the Ca
2+
signaling in response to flow and it provides a general mechanistic explanation for the stimulatory role of blood-borne agonists on flow-induced Ca
2+
influx.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
60 articles.
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