Ca 2+ Sparks and Their Function in Human Cerebral Arteries

Stroke - Tập 33 Số 3 - Trang 802-808 - 2002
George C. Wellman1, David J. Nathan1, Christine M. Saundry1, Guillermo J. Pérez1, Adrian D. Bonev1, Paul L. Penar1, Bruce I. Tranmer1, Mark T. Nelson1
1From 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.

Tóm tắt

Background and Purpose — Local Ca 2+ release events (Ca 2+ sparks) caused by the opening of ryanodine-sensitive Ca 2+ channels in the sarcoplasmic reticulum have been suggested to oppose constriction in cerebral arteries through the activation of large-conductance Ca 2+ -activated K + (BK) channels. We report the first identification and characterization of Ca 2+ sparks and associated BK channel currents in smooth muscle cells isolated from human cerebral arteries. Methods — Membrane currents and intracellular Ca 2+ were measured with the use of the patch-clamp technique and laser scanning confocal microscopy. Results — Ca 2+ sparks with a peak fractional fluorescence change (F/F 0 ) of 2.02±0.04 and size of 8.2±0.5 μm 2 (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 2+ sparks (61 of 85 sparks) were associated with transient BK currents. Consistent with a role for Ca 2+ sparks in the control of cerebral artery diameter, agents that block Ca 2+ sparks (ryanodine) or BK channels (iberiotoxin) were found to contract human cerebral arteries. Conclusions — This study provides evidence for local Ca 2+ signaling in human arterial myocytes and suggests that these events may play an important role in control of cerebral artery diameter in humans.

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Stroke

Tập 33 Số 3

802-808

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