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.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.