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© The Rockefeller University Press, 0021-9525/2002/7/193-a $5.00
The Journal of Cell Biology, Volume 158, Number 2, July 22, 2002 193-a-193

Watching Ca²⁺ waves break

CICR occurs after uncaging calcium at apical (red) but not basal (blue) locations.

Most models of intracellular Ca²⁺ signaling invoke calcium-induced calcium release (CICR), a positive feedback mechanism that amplifies small elevations in cytoplasmic Ca²⁺ to produce complex signals. But what determines the pattern of signaling, and how does a cell avoid triggering Ca²⁺ release in the wrong place? Ashby et al., reporting on page 283, addressed these questions with a powerful new technique and arrived at some surprising conclusions.

Using spatially restricted uncaging of caged Ca²⁺, the authors were able to boost cytosolic Ca²⁺ concentrations in specific regions within pancreatic acinar cells. These cells ordinarily produce polarized Ca²⁺ waves after stimulation with an agonist. When caged Ca²⁺ uncaged in the apical region of the cells, a CICR wave spreads from the apical region toward the basal membrane. In contrast, uncaging Ca²⁺ in the basal region does not produce a CICR wave at all.

CICR is usually associated with ryanodine receptors, which are found in both the apical and basal regions of these cells. However, Ashby et al. found that inhibitors of either ryanodine receptors or IP3 receptors block the induced waves, indicating that CICR requires cooperation between both types of Ca²⁺ release channels. As IP3 receptors are restricted to the apical region, a CICR wave can only be induced there. Ca²⁺ uncaging did not stimulate IP3 production, so participation of the IP3 receptors in CICR wave generation does not require elevation of the IP3 concentration.

Although CICR waves could not be initiated in the basal region, waves that originate in the apical region can travel through the basal region. One possibility is that Ca²⁺ channels may be closely spaced along "gunpowder trails" in the basal region, allowing a signal that originated elsewhere to propagate along a route with a high density of Ca²⁺-sensitive and Ca²⁺- releasing sites. Such a system would help determine the pattern of Ca²⁺ signaling while preventing Ca²⁺ release in the wrong part of the cell.

Alan W. Dove

alanwdove{at}earthlink.net

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Localized Ca²⁺ uncaging reveals polarized distribution of Ca²⁺-sensitive Ca²⁺ release sites: mechanism of unidirectional Ca²⁺ waves

Michael C. Ashby, Madeleine Craske, Myoung Kyu Park, Oleg V. Gerasimenko, Robert D. Burgoyne, Ole H. Petersen, and Alexei V. Tepikin
J. Cell Biol. 2002 158: 283-292. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 440K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?