Role of Na+-K+-2Cl- Cotransporter 1 in Phenylephrine-Induced Rhythmic Contraction in the Mouse Aorta: Regulation of Na+-K+-2Cl- Cotransporter 1 by Ca2+ Sparks and KCa 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 Citations (Scopus)

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 Ca2+-activated K+ channel blocker TEA and iberiotoxin increased the amplitude of PE-induced rhythmic contraction. The voltage-dependent Ca2+ channel blocker, nifedipine, and a Ca2+-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 Ca2+-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
Externally publishedYes

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Phenylephrine
Aorta
Bumetanide
Niflumic Acid
Ryanodine
Ryanodine Receptor Calcium Release Channel
Vasoconstrictor Agents
Nifedipine
Vascular Smooth Muscle
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Calcium-Activated Potassium Channels
Gap Junctions
Sarcoplasmic Reticulum
Thoracic Aorta
Membrane Potentials
Smooth Muscle Myocytes
Veins
Buffers
Arteries

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Role of Na+-K+-2Cl- Cotransporter 1 in Phenylephrine-Induced Rhythmic Contraction in the Mouse Aorta : Regulation of Na+-K+-2Cl- Cotransporter 1 by Ca2+ Sparks and KCa Channels. / Shen, Bing; Fu, Jie; Guo, Jizheng; Zhang, Jie; Wang, Xia; Pan, Xiang; Chen, Meihua; Zhou, Yifan; Zhu, Min; Du, Juan.

In: Cellular Physiology and Biochemistry, Vol. 37, No. 2, 28.08.2015, p. 747-758.

Research output: Contribution to journalArticle

Shen, Bing ; Fu, Jie ; Guo, Jizheng ; Zhang, Jie ; Wang, Xia ; Pan, Xiang ; Chen, Meihua ; Zhou, Yifan ; Zhu, Min ; Du, Juan. / Role of Na+-K+-2Cl- Cotransporter 1 in Phenylephrine-Induced Rhythmic Contraction in the Mouse Aorta : Regulation of Na+-K+-2Cl- Cotransporter 1 by Ca2+ Sparks and KCa Channels. In: Cellular Physiology and Biochemistry. 2015 ; Vol. 37, No. 2. pp. 747-758.
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T1 - Role of Na+-K+-2Cl- Cotransporter 1 in Phenylephrine-Induced Rhythmic Contraction in the Mouse Aorta

T2 - Regulation of Na+-K+-2Cl- Cotransporter 1 by Ca2+ Sparks and KCa Channels

AU - Shen, Bing

AU - Fu, Jie

AU - Guo, Jizheng

AU - Zhang, Jie

AU - Wang, Xia

AU - Pan, Xiang

AU - Chen, Meihua

AU - Zhou, Yifan

AU - Zhu, Min

AU - Du, Juan

PY - 2015/8/28

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N2 - 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 Ca2+-activated K+ channel blocker TEA and iberiotoxin increased the amplitude of PE-induced rhythmic contraction. The voltage-dependent Ca2+ channel blocker, nifedipine, and a Ca2+-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 Ca2+-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.

AB - 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 Ca2+-activated K+ channel blocker TEA and iberiotoxin increased the amplitude of PE-induced rhythmic contraction. The voltage-dependent Ca2+ channel blocker, nifedipine, and a Ca2+-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 Ca2+-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.

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KW - Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> cotransporter 1

KW - Phenylephrine

KW - Rhythmic contraction

KW - Ryanodine receptor

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