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Medientyp:
E-Artikel
Titel:
Ca 2+ Sparks and Their Function in Human Cerebral Arteries
Beteiligte:
Wellman, George C.;
Nathan, David J.;
Saundry, Christine M.;
Perez, Guillermo;
Bonev, Adrian D.;
Penar, Paul L.;
Tranmer, Bruce I.;
Nelson, Mark T.
Beschreibung:
<jats:p>
<jats:bold>
<jats:italic>
<jats:bold>
<jats:italic>Background and Purpose</jats:italic>
</jats:bold>
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</jats:italic>
</jats:bold>
Local Ca
<jats:sup>2+</jats:sup>
release events (Ca
<jats:sup>2+</jats:sup>
sparks) caused by the opening of ryanodine-sensitive Ca
<jats:sup>2+</jats:sup>
channels in the sarcoplasmic reticulum have been suggested to oppose constriction in cerebral arteries through the activation of large-conductance Ca
<jats:sup>2+</jats:sup>
-activated K
<jats:sup>+</jats:sup>
(BK) channels. We report the first identification and characterization of Ca
<jats:sup>2+</jats:sup>
sparks and associated BK channel currents in smooth muscle cells isolated from human cerebral arteries.
</jats:p>
<jats:p>
<jats:bold>
<jats:italic>
<jats:bold>
<jats:italic>Methods</jats:italic>
</jats:bold>
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</jats:italic>
</jats:bold>
Membrane currents and intracellular Ca
<jats:sup>2+</jats:sup>
were measured with the use of the patch-clamp technique and laser scanning confocal microscopy.
</jats:p>
<jats:p>
<jats:bold>
<jats:italic>
<jats:bold>
<jats:italic>Results</jats:italic>
</jats:bold>
—
</jats:italic>
</jats:bold>
Ca
<jats:sup>2+</jats:sup>
sparks with a peak fractional fluorescence change (F/F
<jats:sub>0</jats:sub>
) of 2.02±0.04 and size of 8.2±0.5 μm
<jats:sup>2</jats:sup>
(n=108) occurred at a frequency of approximately 1 Hz in freshly isolated, cerebral artery myocytes from humans. At a holding potential of −40 mV, the majority of, but not all, Ca
<jats:sup>2+</jats:sup>
sparks (61 of 85 sparks) were associated with transient BK currents. Consistent with a role for Ca
<jats:sup>2+</jats:sup>
sparks in the control of cerebral artery diameter, agents that block Ca
<jats:sup>2+</jats:sup>
sparks (ryanodine) or BK channels (iberiotoxin) were found to contract human cerebral arteries.
</jats:p>
<jats:p>
<jats:bold>
<jats:italic>
<jats:bold>
<jats:italic>Conclusions</jats:italic>
</jats:bold>
—
</jats:italic>
</jats:bold>
This study provides evidence for local Ca
<jats:sup>2+</jats:sup>
signaling in human arterial myocytes and suggests that these events may play an important role in control of cerebral artery diameter in humans.
</jats:p>