期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 28, 页码 9627-9632出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0801963105
关键词
calcium; endothelium; calcium biosensor; intermediate conductance; Ca2+-sensitive potassium channel; calcium pulsar
资金
- NHLBI NIH HHS [HL77378, P01 HL077378, HL44455, R01 HL044455, R01 HL045239, HL45239] Funding Source: Medline
- NIDDK NIH HHS [R01 DK053832, R01 DK058795, R01 DK065947, DK65992, DK65947, DK53832, DK58795, R01 DK065992, R37 DK053832] Funding Source: Medline
Calcium (Ca2+) release through inositol 1,4,5-trisphosphate receptors (IP(3)Rs) regulates the function of virtually every mammalian cell. Unlike ryanodine receptors, which generate local Ca2+ events (sparks) that transmit signals to the juxtaposed cell membrane, a similar functional architecture has not been reported for IP(3)Rs. Here, we have identified spatially fixed, local Ca2+ release events (Pulsars) in vascular endothelial membrane domains that project through the internal elastic lamina to adjacent smooth muscle membranes. Ca2+ pulsars are mediated by IP(3)Rs in the endothelial endoplasmic reticulum of these membrane projections. Elevation of IP3 by the endothelium-dependent vasodilator, acetylcholine, increased the frequency of Ca2+ pulsars, whereas blunting IN production, blocking IP(3)Rs, or depleting endoplasmic reticulum Ca2+ inhibited these events. The elementary properties of Ca2+ pulsars were distinct from ryanodine-receptor-mediated Ca2+ sparks in smooth muscle and from IP3-mediated Ca2+ puffs in Xenopus oocytes. The intermediate conductance, Ca2+-sensitive potassium (K(Ca)3.1) channel also colocalized to the endothelial projections, and blockage of this channel caused an 8-mV depolarization. Inhibition of Ca2+ pulsars also depolarized to a similar extent, and blocking K(Ca)3.1 channels was without effect in the absence of pulsars. Our results support a mechanism of IP3 signaling in which Ca2+ release is spatially restricted to transmit intercellular signals.
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