Hormone-evoked elementary Ca²⁺ signals are not stereotypic, but reflect activation of different size channel clusters and variable recruitment of channels within a cluster

Thomas, David; Lipp, Peter; Berridge, Michael J. and Bootman, Martin D. (1998). Hormone-evoked elementary Ca²⁺ signals are not stereotypic, but reflect activation of different size channel clusters and variable recruitment of channels within a cluster. Journal of Biological Chemistry, 273(42) pp. 27130–27136.

DOI: https://doi.org/10.1074/jbc.273.42.27130

URL: http://www.jbc.org/content/273/42/27130.full.pdf+h...

Abstract

Previous studies of (InsP₃)-evoked elementary Ca²⁺ events suggested a hierarchy of signals; fundamental events ("Ca²⁺ blips") arising from single InsP₃ receptors (InsP₃Rs), and intermediate events ("Ca²⁺+ puffs") reflecting the coordinated opening of a cluster of InsP₃Rs. The characteristics of such elementary Ca²⁺ release signals provide insights into the functional interaction and distribution of InsP₃Rs in living cells. Therefore we investigated whether elementary Ca²⁺ signaling is truly represented by such stereotypic release events. A histogram of >900 events revealed a wide spread of signal amplitudes (20-600 nM; mean 216 ± 4 nM; n = 206 cells), which cannot be explained by stochastic variation of a stereotypic Ca²⁺ release site. We identified elementary Ca²⁺ release sites with consistent amplitudes (<20% difference) and locations with variable amplitudes (~500% difference). Importantly, within single cells, distinct sites displayed events with significantly different mean amplitudes. Additional determinants affecting the magnitude of elementary Ca²⁺ release were identified to be (i) hormone concentration, (ii) day-to-day variability, and (iii) a progressively decreasing Ca²⁺ release during prolonged stimulation. We therefore suggest that elementary Ca²⁺ events are not stereotypic, instead a continuum of signals can be achieved by either recruitment of entire clusters with different numbers of InsP₃Rs or by a graded recruitment of InsP₃Rs within a cluster.

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