Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of α-subunits

Qi Xi, Dilyara Tcheranova, Elena Parfenova, Burton Horowitz, Charles Leffler, Jonathan Jaggar

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Abstract

Carbon monoxide (CO) is a gaseous vasodilator produced by many cell types, including endothelial and smooth muscle cells. The goal of the present study was to investigate signaling mechanisms responsible for CO activation of large-conductance Ca2+-activated K+ (KCa) channels in newborn porcine cerebral arteriole smooth muscle cells. In intact cells at 0 mV, CO (3 μM) or CO released from dimanganese decacarbonyl (10 μM), a novel light-activated CO donor, increased KCa channel activity 4.9-or 3.5-fold, respectively. KCa channel activation by CO was not blocked by 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (25 μM), a soluble guanylyl cyclase inhibitor. In inside-out patches at 0 mV, CO shifted the Ca2+ concentration-response curve for Kca KCa channels leftward and decreased the apparent dissociation constant for Ca 2+ from 31 to 24 μM. Western blotting data suggested that the low Ca2+ sensitivity of newborn KCa channels may be due to a reduced β-subunit-to-α-subunit ratio. CO activation of K Ca channels was Ca2+ dependent. CO increased open probability 3.7-fold with 10 μM free Ca2+ at the cytosolic membrane surface but only 1.1-fold with 300 nM Ca2+. CO left shifted the current-voltage relationship of cslo-α currents expressed in HEK-293 cells, increasing currents 2.2-fold at +50 mV. In summary, data suggest that in newborn arteriole smooth muscle cells, CO activates low-affinity KCa channels via a direct effect on the α-subunit that increases apparent Ca2+ sensitivity. The optimal tuning by CO of the micromolar Ca 2+ sensitivity of KCa channels will lead to preferential activation by signaling modalities, such as Ca2+ sparks, which elevate the subsarcolemmal Ca2+ concentration within this range.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number2 55-2
StatePublished - Feb 1 2004

Fingerprint

Arterioles
Carbon Monoxide
Smooth Muscle Myocytes
Calcium-Activated Potassium Channels
Quinoxalines
HEK293 Cells
Vasodilator Agents
Swine
Endothelial Cells
Western Blotting
Light

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of α-subunits",
abstract = "Carbon monoxide (CO) is a gaseous vasodilator produced by many cell types, including endothelial and smooth muscle cells. The goal of the present study was to investigate signaling mechanisms responsible for CO activation of large-conductance Ca2+-activated K+ (KCa) channels in newborn porcine cerebral arteriole smooth muscle cells. In intact cells at 0 mV, CO (3 μM) or CO released from dimanganese decacarbonyl (10 μM), a novel light-activated CO donor, increased KCa channel activity 4.9-or 3.5-fold, respectively. KCa channel activation by CO was not blocked by 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (25 μM), a soluble guanylyl cyclase inhibitor. In inside-out patches at 0 mV, CO shifted the Ca2+ concentration-response curve for Kca KCa channels leftward and decreased the apparent dissociation constant for Ca 2+ from 31 to 24 μM. Western blotting data suggested that the low Ca2+ sensitivity of newborn KCa channels may be due to a reduced β-subunit-to-α-subunit ratio. CO activation of K Ca channels was Ca2+ dependent. CO increased open probability 3.7-fold with 10 μM free Ca2+ at the cytosolic membrane surface but only 1.1-fold with 300 nM Ca2+. CO left shifted the current-voltage relationship of cslo-α currents expressed in HEK-293 cells, increasing currents 2.2-fold at +50 mV. In summary, data suggest that in newborn arteriole smooth muscle cells, CO activates low-affinity KCa channels via a direct effect on the α-subunit that increases apparent Ca2+ sensitivity. The optimal tuning by CO of the micromolar Ca 2+ sensitivity of KCa channels will lead to preferential activation by signaling modalities, such as Ca2+ sparks, which elevate the subsarcolemmal Ca2+ concentration within this range.",
author = "Qi Xi and Dilyara Tcheranova and Elena Parfenova and Burton Horowitz and Charles Leffler and Jonathan Jaggar",
year = "2004",
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language = "English (US)",
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journal = "American Journal of Physiology",
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TY - JOUR

T1 - Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of α-subunits

AU - Xi, Qi

AU - Tcheranova, Dilyara

AU - Parfenova, Elena

AU - Horowitz, Burton

AU - Leffler, Charles

AU - Jaggar, Jonathan

PY - 2004/2/1

Y1 - 2004/2/1

N2 - Carbon monoxide (CO) is a gaseous vasodilator produced by many cell types, including endothelial and smooth muscle cells. The goal of the present study was to investigate signaling mechanisms responsible for CO activation of large-conductance Ca2+-activated K+ (KCa) channels in newborn porcine cerebral arteriole smooth muscle cells. In intact cells at 0 mV, CO (3 μM) or CO released from dimanganese decacarbonyl (10 μM), a novel light-activated CO donor, increased KCa channel activity 4.9-or 3.5-fold, respectively. KCa channel activation by CO was not blocked by 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (25 μM), a soluble guanylyl cyclase inhibitor. In inside-out patches at 0 mV, CO shifted the Ca2+ concentration-response curve for Kca KCa channels leftward and decreased the apparent dissociation constant for Ca 2+ from 31 to 24 μM. Western blotting data suggested that the low Ca2+ sensitivity of newborn KCa channels may be due to a reduced β-subunit-to-α-subunit ratio. CO activation of K Ca channels was Ca2+ dependent. CO increased open probability 3.7-fold with 10 μM free Ca2+ at the cytosolic membrane surface but only 1.1-fold with 300 nM Ca2+. CO left shifted the current-voltage relationship of cslo-α currents expressed in HEK-293 cells, increasing currents 2.2-fold at +50 mV. In summary, data suggest that in newborn arteriole smooth muscle cells, CO activates low-affinity KCa channels via a direct effect on the α-subunit that increases apparent Ca2+ sensitivity. The optimal tuning by CO of the micromolar Ca 2+ sensitivity of KCa channels will lead to preferential activation by signaling modalities, such as Ca2+ sparks, which elevate the subsarcolemmal Ca2+ concentration within this range.

AB - Carbon monoxide (CO) is a gaseous vasodilator produced by many cell types, including endothelial and smooth muscle cells. The goal of the present study was to investigate signaling mechanisms responsible for CO activation of large-conductance Ca2+-activated K+ (KCa) channels in newborn porcine cerebral arteriole smooth muscle cells. In intact cells at 0 mV, CO (3 μM) or CO released from dimanganese decacarbonyl (10 μM), a novel light-activated CO donor, increased KCa channel activity 4.9-or 3.5-fold, respectively. KCa channel activation by CO was not blocked by 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (25 μM), a soluble guanylyl cyclase inhibitor. In inside-out patches at 0 mV, CO shifted the Ca2+ concentration-response curve for Kca KCa channels leftward and decreased the apparent dissociation constant for Ca 2+ from 31 to 24 μM. Western blotting data suggested that the low Ca2+ sensitivity of newborn KCa channels may be due to a reduced β-subunit-to-α-subunit ratio. CO activation of K Ca channels was Ca2+ dependent. CO increased open probability 3.7-fold with 10 μM free Ca2+ at the cytosolic membrane surface but only 1.1-fold with 300 nM Ca2+. CO left shifted the current-voltage relationship of cslo-α currents expressed in HEK-293 cells, increasing currents 2.2-fold at +50 mV. In summary, data suggest that in newborn arteriole smooth muscle cells, CO activates low-affinity KCa channels via a direct effect on the α-subunit that increases apparent Ca2+ sensitivity. The optimal tuning by CO of the micromolar Ca 2+ sensitivity of KCa channels will lead to preferential activation by signaling modalities, such as Ca2+ sparks, which elevate the subsarcolemmal Ca2+ concentration within this range.

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M3 - Article

VL - 286

JO - American Journal of Physiology

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