Hypoxia reduces K Ca channel activity by inducing Ca 2+ spark uncoupling in cerebral artery smooth muscle cells

Guiling Zhao, Adebowale Adebiyi, Qi Xi, Jonathan Jaggar

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Abstract

Arterial smooth muscle cell large-conductance Ca 2+ -activated potassium (K Ca ) channels have been implicated in modulating hypoxic dilation of systemic arteries, although this is controversial. K Ca channel activity in arterial smooth muscle cells is controlled by localized intracellular Ca 2+ transients, termed Ca 2+ sparks, but hypoxic regulation of Ca 2+ sparks and K Ca channel activation by Ca 2+ sparks has not been investigated. We report here that in voltage-clamped (-40 mV) cerebral artery smooth muscle cells, a reduction in dissolved O 2 partial pressure from 150 to 15 mmHg reversibly decreased Ca 2+ spark-induced transient K Ca current frequency and amplitude to 61% and 76% of control, respectively. In contrast, hypoxia did not alter Ca 2+ spark frequency, amplitude, global intracellular Ca 2+ concentration, or sarcoplasmic reticulum Ca 2+ load. Hypoxia reduced transient K Ca current frequency by decreasing the percentage of Ca 2+ sparks that activated a transient K Ca current from 89% to 63%. Hypoxia reduced transient K Ca current amplitude by attenuating the amplitude relationship between Ca 2+ sparks that remained coupled and the evoked transient K Ca currents. Consistent with these data, in inside-out patches at -40 mV hypoxia reduced K Ca channel apparent Ca 2+ sensitivity and increased the K d for Ca 2+ from ∼17 to 32 μM, but did not alter single-channel amplitude. In summary, data indicate that hypoxia reduces K Ca channel apparent Ca 2+ sensitivity via a mechanism that is independent of cytosolic signaling messengers, and this leads to uncoupling of K Ca channels from Ca 2+ sparks. Transient K Ca current inhibition due to uncoupling would oppose hypoxic cerebrovascular dilation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 1 2007

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Cerebral Arteries
Smooth Muscle Myocytes
Dilatation
Partial Pressure
Sarcoplasmic Reticulum
Potassium
Arteries
Hypoxia

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

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title = "Hypoxia reduces K Ca channel activity by inducing Ca 2+ spark uncoupling in cerebral artery smooth muscle cells",
abstract = "Arterial smooth muscle cell large-conductance Ca 2+ -activated potassium (K Ca ) channels have been implicated in modulating hypoxic dilation of systemic arteries, although this is controversial. K Ca channel activity in arterial smooth muscle cells is controlled by localized intracellular Ca 2+ transients, termed Ca 2+ sparks, but hypoxic regulation of Ca 2+ sparks and K Ca channel activation by Ca 2+ sparks has not been investigated. We report here that in voltage-clamped (-40 mV) cerebral artery smooth muscle cells, a reduction in dissolved O 2 partial pressure from 150 to 15 mmHg reversibly decreased Ca 2+ spark-induced transient K Ca current frequency and amplitude to 61{\%} and 76{\%} of control, respectively. In contrast, hypoxia did not alter Ca 2+ spark frequency, amplitude, global intracellular Ca 2+ concentration, or sarcoplasmic reticulum Ca 2+ load. Hypoxia reduced transient K Ca current frequency by decreasing the percentage of Ca 2+ sparks that activated a transient K Ca current from 89{\%} to 63{\%}. Hypoxia reduced transient K Ca current amplitude by attenuating the amplitude relationship between Ca 2+ sparks that remained coupled and the evoked transient K Ca currents. Consistent with these data, in inside-out patches at -40 mV hypoxia reduced K Ca channel apparent Ca 2+ sensitivity and increased the K d for Ca 2+ from ∼17 to 32 μM, but did not alter single-channel amplitude. In summary, data indicate that hypoxia reduces K Ca channel apparent Ca 2+ sensitivity via a mechanism that is independent of cytosolic signaling messengers, and this leads to uncoupling of K Ca channels from Ca 2+ sparks. Transient K Ca current inhibition due to uncoupling would oppose hypoxic cerebrovascular dilation.",
author = "Guiling Zhao and Adebowale Adebiyi and Qi Xi and Jonathan Jaggar",
year = "2007",
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language = "English (US)",
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T1 - Hypoxia reduces K Ca channel activity by inducing Ca 2+ spark uncoupling in cerebral artery smooth muscle cells

AU - Zhao, Guiling

AU - Adebiyi, Adebowale

AU - Xi, Qi

AU - Jaggar, Jonathan

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Arterial smooth muscle cell large-conductance Ca 2+ -activated potassium (K Ca ) channels have been implicated in modulating hypoxic dilation of systemic arteries, although this is controversial. K Ca channel activity in arterial smooth muscle cells is controlled by localized intracellular Ca 2+ transients, termed Ca 2+ sparks, but hypoxic regulation of Ca 2+ sparks and K Ca channel activation by Ca 2+ sparks has not been investigated. We report here that in voltage-clamped (-40 mV) cerebral artery smooth muscle cells, a reduction in dissolved O 2 partial pressure from 150 to 15 mmHg reversibly decreased Ca 2+ spark-induced transient K Ca current frequency and amplitude to 61% and 76% of control, respectively. In contrast, hypoxia did not alter Ca 2+ spark frequency, amplitude, global intracellular Ca 2+ concentration, or sarcoplasmic reticulum Ca 2+ load. Hypoxia reduced transient K Ca current frequency by decreasing the percentage of Ca 2+ sparks that activated a transient K Ca current from 89% to 63%. Hypoxia reduced transient K Ca current amplitude by attenuating the amplitude relationship between Ca 2+ sparks that remained coupled and the evoked transient K Ca currents. Consistent with these data, in inside-out patches at -40 mV hypoxia reduced K Ca channel apparent Ca 2+ sensitivity and increased the K d for Ca 2+ from ∼17 to 32 μM, but did not alter single-channel amplitude. In summary, data indicate that hypoxia reduces K Ca channel apparent Ca 2+ sensitivity via a mechanism that is independent of cytosolic signaling messengers, and this leads to uncoupling of K Ca channels from Ca 2+ sparks. Transient K Ca current inhibition due to uncoupling would oppose hypoxic cerebrovascular dilation.

AB - Arterial smooth muscle cell large-conductance Ca 2+ -activated potassium (K Ca ) channels have been implicated in modulating hypoxic dilation of systemic arteries, although this is controversial. K Ca channel activity in arterial smooth muscle cells is controlled by localized intracellular Ca 2+ transients, termed Ca 2+ sparks, but hypoxic regulation of Ca 2+ sparks and K Ca channel activation by Ca 2+ sparks has not been investigated. We report here that in voltage-clamped (-40 mV) cerebral artery smooth muscle cells, a reduction in dissolved O 2 partial pressure from 150 to 15 mmHg reversibly decreased Ca 2+ spark-induced transient K Ca current frequency and amplitude to 61% and 76% of control, respectively. In contrast, hypoxia did not alter Ca 2+ spark frequency, amplitude, global intracellular Ca 2+ concentration, or sarcoplasmic reticulum Ca 2+ load. Hypoxia reduced transient K Ca current frequency by decreasing the percentage of Ca 2+ sparks that activated a transient K Ca current from 89% to 63%. Hypoxia reduced transient K Ca current amplitude by attenuating the amplitude relationship between Ca 2+ sparks that remained coupled and the evoked transient K Ca currents. Consistent with these data, in inside-out patches at -40 mV hypoxia reduced K Ca channel apparent Ca 2+ sensitivity and increased the K d for Ca 2+ from ∼17 to 32 μM, but did not alter single-channel amplitude. In summary, data indicate that hypoxia reduces K Ca channel apparent Ca 2+ sensitivity via a mechanism that is independent of cytosolic signaling messengers, and this leads to uncoupling of K Ca channels from Ca 2+ sparks. Transient K Ca current inhibition due to uncoupling would oppose hypoxic cerebrovascular dilation.

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