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      Voltage-Gated Sodium Channels in Human Aortic Smooth Muscle Cells

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          Abstract

          Whole-cell, voltage clamp methods were used to study inward currents in human aortic smooth muscle cells in culture. Cells were plated on glass coverslips, cultured in supplemented M-199 media with 5% serum and studied as primary cells and at passages 2–5. Inward currents were measured with a pipette solution containing Cs<sup>+</sup> and TEA<sup>+</sup> to block K<sup>+</sup> currents and with 2.5 m M [Ca<sup>2+</sup>]₀ in the perfusate. Inward currents activated at about –50 mV, peaked at about –15 mV and reversed at about +30 mV. Values of peak inward current averaged 14.7 ± 3.3 pA/pF and cell capacitance averaged 124 ± 10 pF (n = 35). These currents activated rapidly with a time-to-peak current of 2.4 ± 0.3 ms at a test potential of –10 mV from a holding potential of –80 mV. The current also inactivated rapidly with a time course that could be described by two components with time constants of 1.8 ± 0.2 and 17.8 ± 3.5 ms at –10 mV. The currents decreased when extracellular Na<sup>+</sup> was reduced and were completely inhibited by 50 n M tetrodotoxin (TTX), suggesting that they represented voltage-gated Na<sup>+</sup> currents (I<sub>Na</sub>). Activation curves were characterized with a V<sub>0.5</sub> = –16.6 ± 2.4 mV and a slope factor k = –5.2 ± 0.2 mV while inactivation curves were characterized with a V<sub>0.5</sub> = –60.9 ± 1.7 mV and a slope factor k = 8.8 ± 0.4 mV. Lowering external [Ca<sup>2+</sup>] to zero increased the maximum I<sub>Na</sub>, shifted its voltage dependence in the hyperpolarizing direction and increased the rate of I<sub>Na</sub> inactivation. Increasing external [Ca<sup>2+</sup>] or [Mg<sup>2+</sup>]decreased I<sub>Na</sub> and slowed its rate of inactivation. These studies demonstrate the presence of voltage-gated Na<sup>+</sup> channels with high TTX sensitivity that are modulated by extracellular divalent cations in human aortic smooth muscle cells maintained in cell culture. Window currents were found in the voltage range of –50 to –20 mV, suggesting that these channels could contribute to the resting membrane potential.

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          Most cited references 3

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          • Abstract: not found
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          Comparison of K+ channel properties in freshly isolated myocytes from thoracic aorta of WKY and SHR

           Cox,  R. COX,  R Cox (1996)
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            • Record: found
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            High-affinity binding sites for [3H]saxitoxin are associated with voltage-dependent sodium channels in portal vein smooth muscle

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              Vascular smooth muscle contraction induced by Na+ channel activators, veratridine and batrachotoxin

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                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                1998
                October 1998
                28 October 1998
                : 35
                : 5
                : 310-317
                Affiliations
                Bockus Research Institute, The Graduate Hospital, Department of Physiology, University of Pennsylvania and Departments of Physiology and Surgery, Medical College of Pennsylvania, Philadelphia, Pa., USA
                Article
                25600 J Vasc Res 1998;35:310–317
                10.1159/000025600
                9789111
                © 1998 S. Karger AG, Basel

                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: 41, Pages: 8
                Categories
                Research Paper

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