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Letter to the editor: “Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?”

2007; American Physical Society; Volume: 293; Issue: 3 Linguagem: Inglês

10.1152/ajpheart.00722.2007

1522-1539

Donald G. Welsh, Cam Ha T. Tran, Frances Plane, Shaun L. Sandow,

Nitric Oxide and Endothelin Effects

LETTERS TO THE EDITORLetter to the editor: “Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?”Donald G. Welsh, Cam Ha Tran, Frances Plane, and Shaun SandowDonald G. Welsh, Cam Ha Tran, Frances Plane, and Shaun SandowPublished Online:01 Sep 2007https://doi.org/10.1152/ajpheart.00722.2007MoreFiguresReferencesRelatedInformationPDF (30 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat to the editor: We read with interest the recent article, published in American Journal of Physiology-Heart and Circulatory Physiology, entitled “Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?” (1). In this article, the authors suggest that focal endothelial depolarization activates voltage-gated Na+ (NaV) channels, inducing an electrical propagation that augments Ca2+ influx through T-type Ca2+ channels. An endothelial factor is then produced at sites distal to the point of stimulation, and this in turn hyperpolarizes smooth muscle and initiates arterial dilation. Although an interesting presumption, the cosigned are troubled by the authors' experimental and conceptual approach. This letter broadly highlights these concerns and briefly explores some specific examples.The principal problem with the current study is the inferential nature of the experimental design and the speculative nature of the data analysis. A resonating example of this concern centers on the fact that presumed changes in membrane potential and endothelial Ca2+ are never directly measured but are instead inferred from vasomotor responses. This is a significant oversight given the centrality of the two parameters to the proposed conduction mechanism. In addition to the use of indirect indexes, several key elements of the proposed conduction mechanism remain untested or were presented without appropriate controls. For example, within this study, we are unable to find direct confirmation of T-type Ca2+-channel expression in intact arterial endothelial cells. Likewise, the immunohistochemical evidence for NaV expression is unconvincing, with the authors apparently showing three different NaV subunits present in connective tissue and two cell types that do not generate action potentials. Compounding these concerns are the authors' problematic use of pharmacological agents and their interpretation of the literature. Agents such as bupivicaine, amiloride, and nickel clearly block a range of ion channels and, as such, their application to in vivo preparations is questionable, particularly without carefully calibrated controls. With respect to the literature, the authors do not provide evidence of NaV expression in noncultured/nondisease-state endothelial cells. Likewise, the authors did not resolve how NaV channels, which are inactive at depolarized voltages, generate the current density required to propagate depolarization. Given these overall limitations, it is perhaps not surprising that the authors have come to a disquieting conclusion. In their article, that conclusion centers on a propagated depolarization eliciting hyperpolarization in vascular smooth muscle. This conclusion lies in stark contrast to a vast body of literature where smooth muscle hyperpolarization is known to mirror and follow endothelial hyperpolarization. This twinning of behavior is supported by the expression of myoendothelial gap junctions that are present in small resistance arteries, including the mouse cremaster.In closing, the current study forwards the interesting hypothesis as to how electrical signals in the endothelium conduct along an artery and control vasomotor tone. However, without direct measurement of core parameters and a more accurate presentation of the underlying literature, it is the opinion of the cosigned that this study does not progress beyond the speculative nature of the title.AUTHOR NOTESAddress for reprint requests and other correspondence: D. G. Welsh, Smooth Muscle Research Group, HMRB-G86, Heritage Medical Research Bldg., Univ. of Calgary, 3330 Hospital Dr. NW, Calgary, AL, T2N-4N1, Canada (e-mail: dwelsh@ucalgary.ca) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationREFERENCE1 Figueroa X, Chen CC, Campbell KP, Damon DN, Day KH, Ramos S, Duling BR. Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone? Am J Physiol Heart Circ Physiol May 18, 2007; doi:10.1152/ajpheart.01368.2006.Google Scholar Cited ByVascular mechanotransductionMichael J. 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Tsoukias1 January 2010 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 298, No. 1Effects of distension on airway inflammation and venular P-selectin expressionAigul Moldobaeva, John Jenkins, and Elizabeth Wagner1 November 2008 | American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 295, No. 5 More from this issue > Volume 293Issue 3September 2007Pages H2007-H2007 Copyright & PermissionsCopyright © 2007 by the American Physiological Societyhttps://doi.org/10.1152/ajpheart.00722.2007PubMed17804398History Published online 1 September 2007 Published in print 1 September 2007 Metrics Downloaded 235 times 8 CITATIONS 8 Total citations 1 Recent citation 1.05 Field Citation Ratio 0.17 Relative Citation Ratio publications9supporting0mentioning9contrasting0Smart Citations9090Citing PublicationsSupportingMentioningContrastingView CitationsSee how this article has been cited at scite.aiscite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.