title: Light-triggered modulation of cellular electrical activity by ruthenium diimine nanoswitches.
abstract: 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.
authors: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-2821, USA.
authors: Joyce G
authors: JG
authors: Rohan
authors: Y Rose
authors: YR
authors: Citron
authors: Alec C
authors: AC
authors: Durrell
authors: Lionel E
authors: LE
authors: Cheruzel
authors: Harry B
authors: HB
authors: Gray
authors: Robert H
authors: RH
authors: Grubbs
authors: Mark
authors: M
authors: Humayun
authors: Kathrin L
authors: KL
authors: Engisch
authors: Victor
authors: V
authors: Pikov
authors: Robert H
authors: RH
authors: Chow
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002244:Carbon / Q000737:chemistry / Q000378:metabolism; D000077482:Carbon Fiber; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D019439:Chromaffin Cells / Q000737:chemistry* / Q000378:metabolism; D004563:Electrochemistry; D057809:HEK293 Cells; D006801:Humans; D049449:Luminescence; D051379:Mice; D008810:Mice, Inbred C57BL; D036103:Nanotechnology / Q000379:methods*; D062308:Optogenetics / Q000379:methods; D010775:Photic Stimulation / Q000379:methods*; D012428:Ruthenium / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000077482:Carbon Fiber; D002244:Carbon; D012428:Ruthenium