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Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections.
Ledoux J, Taylor M, Bonev A, Hannah R, Solodushko V, Shui B, Tallini Y, Kotlikoff M, Nelson MT
National Academy of Sciences. Proceedings. 2008;105(28):9627-9632.
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Abstract
Calcium (Ca(2+)) 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 Ca(2+) 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 Ca(2+) release events ("pulsars") in vascular endothelial membrane domains that project through the internal elastic lamina to adjacent smooth muscle membranes. Ca(2+) pulsars are mediated by IP(3)Rs in the endothelial endoplasmic reticulum of these membrane projections. Elevation of IP(3) by the endothelium-dependent vasodilator, acetylcholine, increased the frequency of Ca(2+) pulsars, whereas blunting IP(3) production, blocking IP(3)Rs, or depleting endoplasmic reticulum Ca(2+) inhibited these events. The elementary properties of Ca(2+) pulsars were distinct from ryanodine-receptor-mediated Ca(2+) sparks in smooth muscle and from IP(3)-mediated Ca(2+) puffs in Xenopus oocytes. The intermediate conductance, Ca(2+)-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 Ca(2+) 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 IP(3) signaling in which Ca(2+) release is spatially restricted to transmit intercellular signals.
Keyword(s)
Animals; Inositol 1,4,5-Trisphosphate Receptors; Mice; Signal Transduction; analysis: Calcium; analysis: Potassium Channels, Calcium-Activated; metabolism: Cell Surface Extensions; physiology: Inositol 1,4,5-Trisphosphate; ultrastructure: Endothelium, Vascular; ultrastructure: Myocytes, Smooth Muscle