1. Cell Biology
Download icon

Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes

  1. Fang-Min Lu
  2. Christine Deisl
  3. Donald W Hilgemann  Is a corresponding author
  1. University of Texas Southwestern Medical Center at Dallas, United States
Research Article
  • Cited 8
  • Views 1,333
  • Annotations
Cite this article as: eLife 2016;5:e19267 doi: 10.7554/eLife.19267

Abstract

Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes.

Article and author information

Author details

  1. Fang-Min Lu

    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Christine Deisl

    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Donald W Hilgemann

    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, United States
    For correspondence
    donald.hilgemann@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5288-5133

Funding

NIH Office of the Director (RO1 #1129843)

  • Donald W Hilgemann

Endowed Professor Collaborative Research Support, Charles and Jane Pak Center of Mineral Metabolism and Clinical Research (Collaborative Research Support)

  • Donald W Hilgemann

American Heart Association (Fellowship #30950013)

  • Christine Deisl

The funder (NIH) had no role in study design, data collection, interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Texas Southwestern Medical center at Dallas (Protocol Number: 2015-101114). Euthanasia was performed with flurane and every effort was made to minimize suffering.

Reviewing Editor

  1. David E Clapham, Howard Hughes Medical Institute, Boston Children's Hospital, United States

Publication history

  1. Received: June 29, 2016
  2. Accepted: September 9, 2016
  3. Accepted Manuscript published: September 14, 2016 (version 1)
  4. Version of Record published: October 4, 2016 (version 2)

Copyright

© 2016, Lu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,333
    Page views
  • 225
    Downloads
  • 8
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Human Biology and Medicine
    King Faisal Yambire et al.
    Research Article
    1. Cell Biology
    2. Neuroscience
    Lorena Armijo-Weingart et al.
    Research Article