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Department of Pharmacology

Rossi, AM, Tovey, SC, Rahman, T, Prole, DL, Taylor, CW

Background: Inositol 1,4,5-trisphosphate receptors (IP 3R) are expressed in almost all animal cells. Three mammalian genes encode closely related IP 3R subunits, which assemble into homo- or hetero-tetramers to form intracellular Ca 2 + channels. Scope of the review: In this brief review, we first consider a variety of complementary methods that allow the links between IP 3 binding and channel gating to be defined. How does IP 3 binding to the IP 3-binding core in each IP 3R subunit cause opening of a cation-selective pore formed by residues towards the C-terminal? We then describe methods that allow IP 3, Ca 2 + signals and IP 3R mobility to be examined in intact cells. A final section briefly considers genetic analyses of IP 3R signalling. Major conclusions: All IP 3R are regulated by both IP 3 and Ca 2 +. This allows them to initiate and regeneratively propagate intracellular Ca 2 + signals. The elementary Ca 2 + release events evoked by IP 3 in intact cells are mediated by very small numbers of active IP 3R and the Ca 2 +-mediated interactions between them. The spatial organization of these Ca 2 + signals and their stochastic dependence on so few IP 3Rs highlight the need for methods that allow the spatial organization of IP 3R signalling to be addressed with single-molecule resolution. General significance: A variety of complementary methods provide insight into the structural basis of IP 3R activation and the contributions of IP 3-evoked Ca 2 + signals to cellular physiology. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling. © 2011 Elsevier B.V.

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1 August 2012
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Journal articles
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Biochimica et Biophysica Acta - General Subjects
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