Agonist-evoked Ca2+ wave progression requires Ca2+ and IP3

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McCarron, J.G. and Chalmers, S. and MacMillan, D. and Olson, M.L. (2010) Agonist-evoked Ca2+ wave progression requires Ca2+ and IP3. Journal of Cellular Physiology, 224 (2). pp. 334-344. ISSN 0021-9541 (https://doi.org/10.1002/jcp.22103)

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Abstract

Smooth muscle responds to IP3-generating agonists by producing Ca2+ waves. Here, the mechanism of wave progression has been investigated in voltage-clamped single smooth muscle cells using localized photolysis of caged IP3 and the caged Ca2+ buffer diazo-2. Waves, evoked by the IP3-generating agonist carbachol (CCh), initiated as a uniform rise in cytoplasmic Ca2+ concentration ([Ca2+]c) over a single though substantial length (∼30 µm) of the cell. During regenerative propagation, the wave-front was about 1/3 the length (∼9 µm) of the initiation site. The wave-front progressed at a relatively constant velocity although amplitude varied through the cell; differences in sensitivity to IP3 may explain the amplitude changes. Ca2+ was required for IP3-mediated wave progression to occur. Increasing the Ca2+ buffer capacity in a small (2 µm) region immediately in front of a CCh-evoked Ca2+ wave halted progression at the site. However, the wave front does not progress by Ca2+-dependent positive feedback alone. In support, colliding [Ca2+]c increases from locally released IP3 did not annihilate but approximately doubled in amplitude. This result suggests that local IP3-evoked [Ca2+]c increases diffused passively. Failure of local increases in IP3 to evoke waves appears to arise from the restricted nature of the IP3 increase. When IP3 was elevated throughout the cell, a localized increase in Ca2+ now propagated as a wave. Together, these results suggest that waves initiate over a surprisingly large length of the cell and that both IP3 and Ca2+ are required for active propagation of the wave front to occur.

ORCID iDs

McCarron, J.G. ORCID logoORCID: https://orcid.org/0000-0002-3302-3984, Chalmers, S. ORCID logoORCID: https://orcid.org/0000-0002-8073-7576, MacMillan, D. and Olson, M.L.;
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