Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channelsCitation formats

  • External authors:
  • Kaivan Khavandi
  • Rachael L Baylie
  • Majid Ahmed
  • Viktoria Csato
  • Philip Eaton
  • David C Hill-Eubanks
  • Adrian D Bonev

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Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels. / Khavandi, Kaivan; Baylie, Rachael L; Sugden, Sarah A; Ahmed, Majid; Csato, Viktoria; Eaton, Philip; Hill-Eubanks, David C; Bonev, Adrian D; Nelson, Mark T; Greenstein, Adam S.

In: Science Signaling, Vol. 9, No. 449, 2016, p. ra100.

Research output: Contribution to journalArticlepeer-review

Harvard

Khavandi, K, Baylie, RL, Sugden, SA, Ahmed, M, Csato, V, Eaton, P, Hill-Eubanks, DC, Bonev, AD, Nelson, MT & Greenstein, AS 2016, 'Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels', Science Signaling, vol. 9, no. 449, pp. ra100. https://doi.org/10.1126/scisignal.aaf6625

APA

Khavandi, K., Baylie, R. L., Sugden, S. A., Ahmed, M., Csato, V., Eaton, P., Hill-Eubanks, D. C., Bonev, A. D., Nelson, M. T., & Greenstein, A. S. (2016). Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels. Science Signaling, 9(449), ra100. https://doi.org/10.1126/scisignal.aaf6625

Vancouver

Author

Khavandi, Kaivan ; Baylie, Rachael L ; Sugden, Sarah A ; Ahmed, Majid ; Csato, Viktoria ; Eaton, Philip ; Hill-Eubanks, David C ; Bonev, Adrian D ; Nelson, Mark T ; Greenstein, Adam S. / Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels. In: Science Signaling. 2016 ; Vol. 9, No. 449. pp. ra100.

Bibtex

@article{1b447b53e8d943a29ae6337fcd34543d,
title = "Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels",
abstract = "Activation of Ca(2+)-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca(2+) signals (Ca(2+) sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues. Oxidant-activated PKG was required to trigger Ca(2+) sparks, BK channel activity, and vasodilation in response to pressure. VSMCs from arteries from mice expressing a form of PKG that could not be activated by oxidants showed reduced Ca(2+) spark frequency, and arterial preparations from these mice had decreased pressure-induced activation of BK channels. Thus, the absence of oxidative activation of PKG disabled the BK channel-mediated negative feedback regulation of vasoconstriction. Our results support the concept of a negative feedback control mechanism that regulates arterial diameter through mechanosensitive production of oxidants to activate PKG and enhance Ca(2+) sparks.",
author = "Kaivan Khavandi and Baylie, {Rachael L} and Sugden, {Sarah A} and Majid Ahmed and Viktoria Csato and Philip Eaton and Hill-Eubanks, {David C} and Bonev, {Adrian D} and Nelson, {Mark T} and Greenstein, {Adam S}",
note = "Copyright {\textcopyright} 2016, American Association for the Advancement of Science.",
year = "2016",
doi = "10.1126/scisignal.aaf6625",
language = "English",
volume = "9",
pages = "ra100",
journal = "Science Signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science (A A A S)",
number = "449",

}

RIS

TY - JOUR

T1 - Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels

AU - Khavandi, Kaivan

AU - Baylie, Rachael L

AU - Sugden, Sarah A

AU - Ahmed, Majid

AU - Csato, Viktoria

AU - Eaton, Philip

AU - Hill-Eubanks, David C

AU - Bonev, Adrian D

AU - Nelson, Mark T

AU - Greenstein, Adam S

N1 - Copyright © 2016, American Association for the Advancement of Science.

PY - 2016

Y1 - 2016

N2 - Activation of Ca(2+)-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca(2+) signals (Ca(2+) sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues. Oxidant-activated PKG was required to trigger Ca(2+) sparks, BK channel activity, and vasodilation in response to pressure. VSMCs from arteries from mice expressing a form of PKG that could not be activated by oxidants showed reduced Ca(2+) spark frequency, and arterial preparations from these mice had decreased pressure-induced activation of BK channels. Thus, the absence of oxidative activation of PKG disabled the BK channel-mediated negative feedback regulation of vasoconstriction. Our results support the concept of a negative feedback control mechanism that regulates arterial diameter through mechanosensitive production of oxidants to activate PKG and enhance Ca(2+) sparks.

AB - Activation of Ca(2+)-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca(2+) signals (Ca(2+) sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries. We report that physiological intraluminal pressure within resistance arteries activated cGMP-dependent protein kinase (PKG) in VSMCs through oxidant-induced formation of an intermolecular disulfide bond between cysteine residues. Oxidant-activated PKG was required to trigger Ca(2+) sparks, BK channel activity, and vasodilation in response to pressure. VSMCs from arteries from mice expressing a form of PKG that could not be activated by oxidants showed reduced Ca(2+) spark frequency, and arterial preparations from these mice had decreased pressure-induced activation of BK channels. Thus, the absence of oxidative activation of PKG disabled the BK channel-mediated negative feedback regulation of vasoconstriction. Our results support the concept of a negative feedback control mechanism that regulates arterial diameter through mechanosensitive production of oxidants to activate PKG and enhance Ca(2+) sparks.

U2 - 10.1126/scisignal.aaf6625

DO - 10.1126/scisignal.aaf6625

M3 - Article

C2 - 27729550

VL - 9

SP - ra100

JO - Science Signaling

JF - Science Signaling

SN - 1945-0877

IS - 449

ER -