Vascular smooth muscle BK channels limit ouabain-induced vasocontraction: dual role of the Na/K-ATPase as a hub for Src-kinase and the Na/Ca-exchanger
Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca2+ concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known...
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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 2024
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| In: |
The FASEB journal
Year: 2024, Jahrgang: 38, Heft: 17, Pages: 1-16 |
| ISSN: | 1530-6860 |
| DOI: | 10.1096/fj.202400628RR |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1096/fj.202400628RR Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1096/fj.202400628RR 
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| Verfasserangaben: | Tobias Orth, Anastasia Pyanova, Simon Lux, Peter Kaiser, Isabel Reinheimer, Daniel Løgstrup Nielsen, Josef Ali Khalid, Salomé Rognant, Thomas A. Jepps, Vladimir V. Matchkov, Rudolf Schubert |
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| 245 | 1 | 0 | |a Vascular smooth muscle BK channels limit ouabain-induced vasocontraction |b dual role of the Na/K-ATPase as a hub for Src-kinase and the Na/Ca-exchanger |c Tobias Orth, Anastasia Pyanova, Simon Lux, Peter Kaiser, Isabel Reinheimer, Daniel Løgstrup Nielsen, Josef Ali Khalid, Salomé Rognant, Thomas A. Jepps, Vladimir V. Matchkov, Rudolf Schubert |
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| 520 | |a Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca2+ concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels. Whether BK channels functionally interact in vascular smooth muscle cells with the Na/K-ATPase remains to be elucidated. Thus, this study addressed the hypothesis that BK channels limit ouabain-induced vasocontraction. Rat mesenteric arteries were studied using isometric myography, FURA-2 fluorimetry and proximity ligation assay. The BK channel blocker iberiotoxin potentiated methoxamine-induced contractions. The cardiotonic steroid, ouabain (10−5 M), induced a contractile effect of IBTX at basal tension prior to methoxamine administration and enhanced the pro-contractile effect of IBTX on methoxamine-induced contractions. These facilitating effects of ouabain were prevented by the inhibition of either NCX or Src kinase. Furthermore, inhibition of NCX or Src kinase reduced the BK channel-mediated negative feedback regulation of arterial contraction. The effects of NCX and Src kinase inhibition were independent of each other. Co-localization of the Na/K-ATPase and the BK channel was evident. Our data suggest that BK channels limit ouabain-induced vasocontraction by a dual mechanism involving the NCX and Src kinase signaling. The data propose that the NCX and the Src kinase pathways, mediating the ouabain-induced activation of the BK channel, act in an independent manner. | ||
| 650 | 4 | |a artery | |
| 650 | 4 | |a BK channel | |
| 650 | 4 | |a Na/K-ATPase | |
| 650 | 4 | |a smooth muscle | |
| 650 | 4 | |a vasocontraction | |
| 700 | 1 | |a Pyanova, Anastasia |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Khalid, Josef Ali |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rognant, Salomé |e VerfasserIn |4 aut | |
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