Role of Voltage-Dependent and Ca ²⁺-Activated K ⁺ Channels on the Regulation of Isometric Force in Porcine Coronary Artery

Abstract

We investigated the role of K⁺ channels in the regulation of vascular tone in de-endothelialized porcine coronary artery. Isometric force and intracellular Ca²⁺ ([Ca²⁺]_i) under resting conditions were increased by treatment with 4-aminopyridine (4-AP, 1 m M), an inhibitor of voltage-dependent K⁺ (K_v) channels, but not by tetraethylammonium chloride (TEA, 1 m M) or charybdotoxin (100 n M), both inhibitors of Ca²⁺-activated K⁺ (K_Ca) channels, or glibenclamide (10 μ M), an inhibitor of ATP-sensitive K⁺ channels. Under stimulated conditions with 9,11-dideoxy-11α,9α-epoxymethano-prostaglandin F_2α (U46619), 4-AP as well as TEA or charybdotoxin increased isometric force and [Ca²⁺]_i, but not glibenclamide. 4-AP was the most potent in terms of depolarization of membrane potential compared with TEA or glibenclamide in the presence or absence of EGTA. In the presence of U46619, a high concentration of 4-AP (10 m M) caused a further contraction with oscillations. The force oscillations induced by 4-AP were inhibited by diltiazem (10 μ M), an inhibitor of voltage-dependent Ca²⁺ channels, or TEA (1 m M), but not by glibenclamide (10 μ M). These force oscillations may be associated with the periodic activation of K_Ca channels. These findings suggested that 4-AP-sensitive K_v channels play an important role in the control of vascular tone in both resting and stimulated conditions. Moreover, under stimulated conditions, K_Ca channels also have an important role in the regulation of vascular tone. Dysfunction of these channels induces abnormal vasoconstriction and may be implicated in vascular diseases such as hypertension and vasospasm.

Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 2000

Publication date (Print): February 2000

Publication date (Electronic): 07 March 2000

Volume: 37

Issue: 1

Pages: 16-25

Affiliations

Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA

Article

Publisher ID: 25709 Other ID: J Vasc Res 2000;37:16–25

DOI: 10.1159/000025709

PubMed ID: 10720882

Copyright statement: © 2000 S. Karger AG, Basel

License:

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.

Page count

Figures: 7, References: 49, Pages: 10

Product

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Categories

Subject: Research Paper