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(Stroke. 2002;33:802.)
© 2002 American Heart Association, Inc.

Original Contributions

Ca²⁺ Sparks and Their Function in Human Cerebral Arteries

George C. Wellman, PhD; David J. Nathan, MD; Christine M. Saundry, BS; Guillermo Perez, PhD; Adrian D. Bonev, PhD; Paul L. Penar, MD; Bruce I. Tranmer, MD Mark T. Nelson, PhD

From the Departments of Pharmacology (G.C.W., D.J.N., C.M.S., G.P., A.D.B., P.L.P., M.T.N.) and Surgery (G.C.W., D.J.N., P.L.P., B.I.T.), University of Vermont College of Medicine, Burlington.

Correspondence to George C. Wellman, PhD, Department of Pharmacology, University of Vermont, Given Building, Room B321, 89 Beaumont Ave, Burlington, VT 05405-0068. E-mail gwellman{at}zoo.uvm.edu

Background and Purpose— Local Ca²⁺ release events (Ca²⁺ sparks) caused by the opening of ryanodine-sensitive Ca²⁺ channels in the sarcoplasmic reticulum have been suggested to oppose constriction in cerebral arteries through the activation of large-conductance Ca²⁺-activated K⁺ (BK) channels. We report the first identification and characterization of Ca²⁺ sparks and associated BK channel currents in smooth muscle cells isolated from human cerebral arteries.

Methods— Membrane currents and intracellular Ca²⁺ were measured with the use of the patch-clamp technique and laser scanning confocal microscopy.

Results— Ca²⁺ sparks with a peak fractional fluorescence change (F/F₀) of 2.02±0.04 and size of 8.2±0.5 µm² (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, Ca²⁺ sparks (61 of 85 sparks) were associated with transient BK currents. Consistent with a role for Ca²⁺ sparks in the control of cerebral artery diameter, agents that block Ca²⁺ sparks (ryanodine) or BK channels (iberiotoxin) were found to contract human cerebral arteries.

Conclusions— This study provides evidence for local Ca²⁺ signaling in human arterial myocytes and suggests that these events may play an important role in control of cerebral artery diameter in humans.

Key Words: calcium • cerebral arteries • muscle, smooth, vascular • potassium channels • ryanodine receptor calcium release channel

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