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Updated: Jun 13, 2026
Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
Published on: March 12, 2013
Alterations of Na+/K+-ATPase function in caveolin-1 knockout cardiac fibroblasts
Luis E M Quintas1, Sandrine V Pierre, Lijun Liu
1Department of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, OH 43614-5804, USA.
Abstract:
Recent studies have demonstrated that the Na(+)/K(+)-ATPase is not only an ion pump, but also a membrane receptor that confers the ligand-like effects of cardiotonic steroids (CTS) such as ouabain on protein kinases and cell growth. Because CTS have been implicated in cardiac fibrosis, this study examined the role of caveolae in the regulation of Na(+)/K(+)-ATPase function and CTS signaling in cardiac fibroblasts. In cardiac fibroblasts prepared from wild-type and caveolin-1 knockout [Cav-1(-/-)] mice, we found that the absence of caveolin-1 did not affect total cellular amount or surface expression of Na(+)/K(+)-ATPase alpha1 subunit. However, it did increase ouabain-sensitive (86)Rb(+) uptake. While knockout of caveolin-1 increased basal activities of Src and ERK1/2, it abolished the activation of these kinases induced by ouabain but not angiotensin II. Finally, ouabain stimulated collagen synthesis and cell proliferation in wild type but not Cav-1(-/-) cardiac fibroblasts. Thus, we conclude that caveolae are important for regulating both pumping and signal transducing functions of Na(+)/K(+)-ATPase. While depletion of caveolae increases the pumping function of Na(+)/K(+)-ATPase, it suppresses CTS-induced signal transduction, growth, and collagen production in cardiac fibroblasts.
Insights
Caveolae regulate the Na(+)/K(+)-ATPase pump and signaling. Depleting caveolae boosts pump activity but reduces cardiotonic steroid-induced cardiac fibroblast growth and collagen production.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Membrane Biology
Background:
- The Na(+)/K(+)-ATPase functions as both an ion pump and a receptor for cardiotonic steroids (CTS).
- CTS, like ouabain, influence protein kinases and cell growth, and are implicated in cardiac fibrosis.
- Caveolae are specialized membrane microdomains that may regulate Na(+)/K(+)-ATPase function and CTS signaling.
Purpose of the Study:
- To investigate the role of caveolae in regulating Na(+)/K(+)-ATPase function and CTS signaling in cardiac fibroblasts.
- To determine how caveolin-1 deficiency affects ouabain-induced signaling pathways and cellular responses.
Main Methods:
- Cardiac fibroblasts were isolated from wild-type and caveolin-1 knockout [Cav-1(-/-)] mice.
- Na(+)/K(+)-ATPase alpha1 subunit expression and ouabain-sensitive (86)Rb(+) uptake were measured.
- Activities of Src and ERK1/2 kinases were assessed under basal and stimulated conditions.
- Collagen synthesis and cell proliferation were evaluated in response to ouabain.
Main Results:
- Caveolin-1 deficiency did not alter Na(+)/K(+)-ATPase alpha1 subunit expression but increased ouabain-sensitive (86)Rb(+) uptake.
- Loss of caveolin-1 elevated basal Src and ERK1/2 activity but abolished ouabain-induced activation of these kinases.
- Ouabain stimulated collagen synthesis and proliferation in wild-type fibroblasts but not in Cav-1(-/-) fibroblasts.
Conclusions:
- Caveolae are crucial regulators of both the pumping and signal transducing functions of Na(+)/K(+)-ATPase.
- Caveolae depletion enhances Na(+)/K(+)-ATPase pumping activity.
- Caveolae absence suppresses CTS-induced signal transduction, fibroblast growth, and collagen production.
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