Role of Na + -K + -2Cl - Cotransporter 1 in Phenylephrine-Induced Rhythmic Contraction in the Mouse Aorta: Regulation of Na + -K + -2Cl - Cotransporter 1 by Ca 2+ Sparks and K Ca Channels

Bing Shen, Jie Fu, Jizheng Guo, Jie Zhang, Xia Wang, Xiang Pan, Meihua Chen, Yifan Zhou, Min Zhu, Juan Du

    Research output: Contribution to journalArticle

    4 Scopus citations

    Abstract

    Background/Aims: Vasoconstrictor-induced rhythmic contraction of arteries or veins has been observed both in vivo and in vitro. Many studies have reported that gap junctions, ryanodine receptors, Na + , K + -ATPase and other factors are involved in vasoconstrictor-induced rhythmic contraction in vascular smooth muscle. However, the mechanism is still not completely understood. Methods: We used vessel tension measurements, intracellular recordings and intracellular Cl - concentration ([Cl - ] i ) measurements to investigate the mechanism underlying phenylephrine (PE)-induced rhythmic contraction in the mouse aorta. Results: We found that Na + -K + -2Cl - cotransporter 1 (NKCC1) inhibitor bumetanide abolished PE-induced rhythmic contraction. The Cl - channel blockers DIDS and niflumic acid initially augmented the amplitude of PE-induced rhythmic contraction but later inhibited the rhythmic contraction. The large Ca 2+ -activated K + channel blocker TEA and iberiotoxin increased the amplitude of PE-induced rhythmic contraction. The voltage-dependent Ca 2+ channel blocker, nifedipine, and a Ca 2+ -free solution abolished PE-induced rhythmic contraction. The inhibitor of ryanodine receptors in the sarcoplasmic reticulum, ryanodine, inhibited PE-induced rhythmic contraction. Moreover, bumetanide hyperpolarized the membrane potential of vascular smooth muscle cells in a resting state or after PE pre-treatment. Bumetanide, niflumic acid, ryanodine, iberiotoxin, nifedipine and Ca 2+ -free buffer significantly suppressed the PE-induced [Cl - ] i increase. Conclusion: These data indicate that NKCC1 is involved in the formation of PE-induced rhythmic contraction, and we also provide a method with which to indirectly observe the NKCC1 activity in isolated intact mouse thoracic aortas.

    Original languageEnglish (US)
    Pages (from-to)747-758
    Number of pages12
    JournalCellular Physiology and Biochemistry
    Volume37
    Issue number2
    DOIs
    StatePublished - Aug 28 2015

    Keywords

    • Aorta
    • Ca2+ sparks
    • KCa channels
    • Na -K -2Cl cotransporter 1
    • Phenylephrine
    • Rhythmic contraction
    • Ryanodine receptor

    ASJC Scopus subject areas

    • Physiology

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