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Light-Triggered Modulation of Cellular Electrical Activity by Ruthenium Diimine Nanoswitches

Rohan, Joyce G. and Citron, Y. Rose and Durrell, Alec C. and Cheruzel, Lionel E. and Gray, Harry B. and Grubbs, Robert H. and Humayun, Mark and Engisch, Kathrin L. and Pikov, Victor and Chow, Robert H. (2013) Light-Triggered Modulation of Cellular Electrical Activity by Ruthenium Diimine Nanoswitches. ACS Chemical Neuroscience, 4 (4). pp. 585-593. ISSN 1948-7193. PMCID PMC3629747.

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Ruthenium diimine complexes have previously been used to facilitate light-activated electron transfer in the study of redox metalloproteins. Excitation at 488 nm leads to a photoexcited state, in which the complex can either accept or donate an electron, respectively, in the presence of a soluble sacrificial reductant or oxidant. Here, we describe a novel application of these complexes in mediating light-induced changes in cellular electrical activity. We demonstrate that RubpyC17 ([Ru(bpy)_(2)(bpy-C17)]^(2+), where bpy is 2,2′-bipyridine and bpy-C17 is 2,2′-4-heptadecyl-4′-methyl-bipyridine), readily incorporates into the plasma membrane of cells, as evidenced by membrane-confined luminescence. Excitable cells incubated in RubpyC17 and then illuminated at 488 nm in the presence of the reductant ascorbate undergo membrane depolarization leading to firing of action potentials. In contrast, the same experiment performed with the oxidant ferricyanide, instead of ascorbate, leads to hyperpolarization. These experiments suggest that illumination of membrane-associated RubpyC17 in the presence of ascorbate alters the cell membrane potential by increasing the negative charge on the outer face of the cell membrane capacitor, effectively depolarizing the cell membrane. We rule out two alternative explanations for light-induced membrane potential changes, using patch clamp experiments: (1) light-induced direct interaction of RubpyC17 with ion channels and (2) light-induced membrane perforation. We show that incorporation of RubpyC17 into the plasma membrane of neuroendocrine cells enables light-induced secretion as monitored by amperometry. While the present work is focused on ruthenium diimine complexes, the findings point more generally to broader application of other transition metal complexes to mediate light-induced biological changes.

Item Type:Article
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URLURL TypeDescription CentralArticle
Gray, Harry B.0000-0002-7937-7876
Grubbs, Robert H.0000-0002-0057-7817
Additional Information:© 2013 American Chemical Society. ACS AuthorChoice. Received: November 27, 2012; Accepted: January 18, 2013; Published: February 18, 2013. Published In Issue April 17, 2013. The present work was supported by the following funding agencies NSF ERC EEC-0310723 (M.H., R.H.C.), Beckman Initiative for Macular Research Grant 1113 (V.P., R.H.C.), Doheny Eye Institute through the Arnold and Mabel Beckman Foundation (M.H., R.H.G.), NIH RO1 GM85791 (R.H.C.), NIH DK019038 (H.B.G.), and NIH F32GM088967 (J.G.R.). Author Contributions: J.G.R. and Y.R.C. contributed equally to the manuscript. M.H. and R.H.C. designed the study. A.C.D. and L.E.C. synthesized and characterized the ruthenium-diimine compound. J.G.R. and Y.R.C. conducted the electrophysiological and imaging experiments. J.G.R., Y.R.C., and R.H.C. wrote the manuscript. All authors participated in the discussion of data and revision of manusccript. The authors declare no competing financial interest.
Funding AgencyGrant Number
Doheny Eye Institute1113
Arnold and Mabel Beckman FoundationUNSPECIFIED
NIHRO1 GM85791
NIH Postdoctoral FellowshipF32GM088967
Beckman Initiative for Macular Research1113
Subject Keywords:Optogenetics; metal-diimine; action potentials; neuroendocrine cells; secretion; light
Issue or Number:4
PubMed Central ID:PMC3629747
Record Number:CaltechAUTHORS:20130523-115225576
Persistent URL:
Official Citation:Light-Triggered Modulation of Cellular Electrical Activity by Ruthenium Diimine Nanoswitches Joyce G. Rohan, Y. Rose Citron, Alec C. Durrell, Lionel E. Cheruzel, Harry B. Gray, Robert H. Grubbs, Mark Humayun, Kathrin L. Engisch, Victor Pikov, and Robert H. Chow ACS Chemical Neuroscience 2013 4 (4), 585-593
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:38660
Deposited By: Jason Perez
Deposited On:24 May 2013 15:10
Last Modified:22 Nov 2019 09:58

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