Potentiation of Acetylcholine-lnduced Responses in Freshly Isolated Rabbit Aortic Endothelial Cells

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Abstract
Acetylcholine (ACh)-induced membrane hyperpolarization was studied in freshly isolated endothelial cells from rabbit aorta. Ten µM ACh induced transient hyperpolarization due to the opening of Ca2+-sensitive K+ channels, sensitive to TEA and charybdotoxin (CTX). The membrane potential response was accompanied by an increase in intracellular Ca2+ [Ca2+]i. Pretreatment of endothelial cells with 20 µM ATP, 0.2 µM bradykinin or 0.1 µM platelet-aggregating factor, which induced either a transient hyperpolarization or no response, changed the subsequent ACh-induced response to a large maintained hyperpolarization. This sustained membrane hyperpolarization was also due to the opening of Ca2+-activated K+ channels as confirmed by CTX and TEA blockade, and was related to elevated [Ca2+]i measured by fura-2 fluorescence. Pertussis toxin blocked potentiation, indicating involvement of a G protein. The linkage to receptor-operated Ca2+ (ROC)-entry was suggested by observations that the maintained hyperpolarization during potentiation was dependent on extracellular Ca2+ and was abolished by the ROC blockers SKF-96365 and Ni2+. Inhibition of the Ca2+ pump of the endoplasmic reticulum mimicked the potentiating effect of the agonists. The results suggest that crosstalk between the agonists in endothelial cells involves Ca2+ movements and that this crosstalk is important for the generation of endothelial secretions.

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