Vascular Regulation via KIR Channels and Na+ /K+-ATPase

Author(s)

Anne R. Crecelius, University of DaytonFollow
Frank A. Dinenno, Colorado State University - Fort Collins

Document Type

Article

Publication Date

7-2015

Publication Source

Channels

Abstract

Despite the longstanding knowledge that blood flow increases in proportion to metabolic activity of skeletal muscle, the underlying mechanisms that govern this response have only recently been identified.¹ Given the role of endothelial cells in mediating exercise hyperemia,² interest has been focused on endothelium-derived vasodilation occurring via the synthesis of nitric oxide (NO) and vasodilating prostaglandins (PGs; i.e. prostacyclin) or endothelium- derived hyperpolarization. A number of studies performed in humans have established a minimal-to-modest role for NO and PGs during mild- and moderate- intensity exercise. In animal preparations, prevention of hyperpolarization attenuates contraction-induced hyperemia; however, performing similar studies in humans has been difficult. Specific candidate contributors to hyperpolarization such as P450 metabolites, calcium-activated potassium (K_Ca) channels, and ATP-sensitive potassium (K_ATP) channels have been inhibited with minimal to nonexistent effects. Recently, we inhibited K_IR channels and Na⁺/K⁺-ATPase [via intraarterial barium chloride (BaCl2) and ouabain] in the human forearm during rhythmic muscle contractions.³ Importantly, we have established that K⁺-mediated vasodilation (intra-arterial infusion of KCl) is essentially abolished following BaCl2 and ouabain administration, evidence of successful inhibition of K_IR channels and Na⁺/K⁺-ATPase. Based on the observed reduction in forearm blood flow during contractions with BaCl₂, we concluded that activation of K_IR channels significantly contributes (~30%) to exercise hyperemia in healthy humans. A reduction of this magnitude is profound, particularly in a small muscle mass such as the forearm.

Inclusive pages

171-172

ISBN/ISSN

1933-6950

Document Version

Published Version

Comments

The item available for download is an open-access autocommentary to:

• Crecelius AR, et al. Contracting human skeletal muscle maintains the ability to blunt a1 -adrenergic vasoconstriction during K_IR channel and Na⁺ /K⁺-ATPase inhibition. J Physiol 2015; 593(12):2735-51; PMID: 25893955; http://dx.doi.org/10.1113/JP270461

It is also openly accessible via the publisher's website.

Permission documentation is on file.

Copyright

Copyright © 2015, Taylor & Francis Group from Vascular Regulation via KIR Channels and Na+ /K+-ATPase by Anne R. Crecelius and Frank A. Dinenno. Reproduced by permission of Taylor and Francis Group, LLC, a division of Informa plc. This material is strictly for personal use. For any other use, the user must contact Taylor & Francis directly at this address: permissions.mailbox@taylorandfrancis.com. Printing, photocopying and sharing via any means is a violation of copyright.

Publisher

Taylor & Francis

Volume

9

Issue

4

Peer Reviewed

yes

Keywords

adrenergic, exercise, humans, muscle contraction, sympatholysis, vasoconstriction

eCommons Citation

Crecelius, Anne R. and Dinenno, Frank A., "Vascular Regulation via KIR Channels and Na+ /K+-ATPase" (2015). Health and Sport Science Faculty Publications. 55.
https://ecommons.udayton.edu/hss_fac_pub/55