Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels

Toshinori Hoshi, Bianka Wissuwa, Yutao Tian, Nobuyoshi Tajima, Rong Xu, Michael Bauer, Stefan H. Heinemann, and Shangwei Hou
PNAS March 19, 2013 110 (12) 4816-4821; https://doi.org/10.1073/pnas.1221997110
Toshinori Hoshi
aDepartment of Physiology, University of Pennsylvania, Philadelphia, PA 19104;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: hoshi@hoshi.org
Bianka Wissuwa
bCenter for Sepsis Control and Care, Jena University Hospital, D-07747 Jena, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yutao Tian
aDepartment of Physiology, University of Pennsylvania, Philadelphia, PA 19104;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nobuyoshi Tajima
aDepartment of Physiology, University of Pennsylvania, Philadelphia, PA 19104;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rong Xu
aDepartment of Physiology, University of Pennsylvania, Philadelphia, PA 19104;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Bauer
bCenter for Sepsis Control and Care, Jena University Hospital, D-07747 Jena, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefan H. Heinemann
cCenter for Molecular Biomedicine, Department of Biophysics, Friedrich Schiller University and Jena University Hospital, D-07745 Jena, Germany; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shangwei Hou
dKey Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  1. Edited by Ramon Latorre, Centro Interdisciplinario de Neurociencias, Universidad de Valparaíso, Valparaíso, Chile, and approved February 1, 2013 (received for review December 17, 2012)

This article has a Letter. Please see:

  • Docosahexaenoic acid ethyl esters ineffective? - May 13, 2013

See related content:

  • DHA and BK channels
    - Mar 04, 2013

See related content:

  • Omega-3 fatty and their derivatives
    - May 13, 2013
  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Abstract

Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA), found abundantly in oily fish, may have diverse health-promoting effects, potentially protecting the immune, nervous, and cardiovascular systems. However, the mechanisms underlying the purported health-promoting effects of DHA remain largely unclear, in part because molecular signaling pathways and effectors of DHA are only beginning to be revealed. In vascular smooth muscle cells, large-conductance Ca2+- and voltage-activated K+ (BK) channels provide a critical vasodilatory influence. We report here that DHA with an EC50 of ∼500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit β1, increasing currents by up to ∼20-fold. The DHA action is observed in cell-free patches and does not require voltage-sensor activation or Ca2+ binding but involves destabilization of the closed conformation of the ion conduction gate. DHA lowers blood pressure in anesthetized wild-type but not in Slo1 knockout mice. DHA ethyl ester, contained in dietary supplements, fails to activate BK channels and antagonizes the stimulatory effect of DHA. Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids, and these fatty acids—unlike their ethyl ester derivatives—activate the channels and lower blood pressure. This finding has practical implications for the use of omega-3 fatty acids as nutraceuticals for the general public and also for the critically ill receiving omega-3–enriched formulas.

  • fish oil
  • lipids
  • KCa1.1
  • immunonutrition

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: hoshi{at}hoshi.org.
  • Author contributions: T.H., Y.T., N.T., M.B., S.H.H., and S.H. designed research; T.H., B.W., Y.T., N.T., R.X., and S.H. performed research; T.H., Y.T., N.T., M.B., S.H.H., and S.H. analyzed data; and T.H., Y.T., N.T., M.B., S.H.H., and S.H. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1221997110/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Omega-3 fatty acids and BK channels
Toshinori Hoshi, Bianka Wissuwa, Yutao Tian, Nobuyoshi Tajima, Rong Xu, Michael Bauer, Stefan H. Heinemann, Shangwei Hou
Proceedings of the National Academy of Sciences Mar 2013, 110 (12) 4816-4821; DOI: 10.1073/pnas.1221997110

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Omega-3 fatty acids and BK channels
Toshinori Hoshi, Bianka Wissuwa, Yutao Tian, Nobuyoshi Tajima, Rong Xu, Michael Bauer, Stefan H. Heinemann, Shangwei Hou
Proceedings of the National Academy of Sciences Mar 2013, 110 (12) 4816-4821; DOI: 10.1073/pnas.1221997110
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 110 (12)
Table of Contents

Submit

Sign up for Article Alerts

Article Classifications

  • Biological Sciences
  • Physiology

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Scientist looking at an electronic tablet
Opinion: Standardizing gene product nomenclature—a call to action
Biomedical communities and journals need to standardize nomenclature of gene products to enhance accuracy in scientific and public communication.
Image credit: Shutterstock/greenbutterfly.
One red and one yellow modeled protein structures
Journal Club: Study reveals evolutionary origins of fold-switching protein
Shapeshifting designs could have wide-ranging pharmaceutical and biomedical applications in coming years.
Image credit: Acacia Dishman/Medical College of Wisconsin.
White and blue bird
Hazards of ozone pollution to birds
Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490