Photochemical Gating of Intracellular Ca2+ Release Channels
Journal of the American Chemical Society2007Vol. 129(17), pp. 5316–5317
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Jiahong Ni, Darryl A. Auston, David A. Freilich, Sukumaran Muralidharan, Eric A. Sobie, Joseph P. Y. Kao
Abstract
We have synthesized BiNiX, a caged methylxanthine agonist for the ryanodine receptor (RyR)the major calcium channel that mediates Ca2+ release from intracellular Ca2+ stores in electrically excitable cells. BiNiX is easily loaded into living cells through incubation with its acetoxymethyl (AM) ester. Delivery of focused UV light pulses to the loaded cell releases paraxanthine focally and rapidly to activate RyRs to release Ca2+, thus elevating intracellular Ca2+ concentration to initiate Ca2+-dependent signaling cascades. We demonstrate the biological utility of BiNiX in heart muscle cells by showing that local intracellular photolysis of BiNiX triggers Ca2+ release and consequent muscle contraction.
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