title: New near-infrared optical probes of cardiac electrical activity.
abstract: Styryl voltage-sensitive dyes (e.g., di-4-ANEPPS) have been widely and successfully used as probes for mapping membrane potential changes in cardiac cells and tissues. However, their utility has been somewhat limited because their excitation wavelengths have been restricted to the 450- to 550-nm range. Longer excitation/emission wavelength probes can minimize interference from endogenous chromophores and, because of decreased light scattering and lower absorption by endogenous chromophores, improve recording from deeper tissue layers. In this article, we report efforts to develop new potentiometric styryl dyes that have excitation wavelengths ranging above 700 nm and emission spectra extending to 900 nm. Three dyes for cardiac optical mapping were investigated in depth from several hundred dyes containing 47 variants of the styryl chromophores. Absorbance and emission spectra in ethanol and multilamellar vesicles, as well as voltage-dependent spectral changes in a model lipid bilayer, have been recorded for these dyes. Optical action potentials were recorded in typical cardiac tissues (rat, guinea pig, pig) and compared with those of di-4-ANEPPS. The voltage sensitivities of the fluorescence of these new potentiometric indicators are as good as those of the widely used ANEP series of probes. In addition, because of molecular engineering of the chromophore, the new dyes provide a wide range of dye loading and washout time constants. These dyes will enable a series of new experiments requiring the optical probing of thick and/or blood-perfused cardiac tissues.
authors.affiliation: Department of Pharmacology, State University of New York-Upstate Medical University, 750 E Adams St., Syracuse, NY 13210, USA. matiukaa@upstate.edu
authors.forename: Arvydas
authors.initials: A
authors.lastname: Matiukas
authors.forename: Bogdan G
authors.initials: BG
authors.lastname: Mitrea
authors.forename: Arkady M
authors.initials: AM
authors.lastname: Pertsov
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Wuskell
authors.forename: Mei-de
authors.initials: MD
authors.lastname: Wei
authors.forename: James
authors.initials: J
authors.lastname: Watras
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Millard
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Loew
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004396:Coloring Agents / Q000737:chemistry*; D004562:Electrocardiography; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008567:Membranes, Artificial; D018408:Patch-Clamp Techniques; D011199:Potentiometry; D011726:Pyridinium Compounds; D051381:Rats; D013045:Species Specificity; D019265:Spectroscopy, Near-Infrared; D013552:Swine
chemical_list: D004396:Coloring Agents; D008567:Membranes, Artificial; D011726:Pyridinium Compounds; C050019:1-(3-sulfonatopropyl)-4-(beta)(2-(di-n-butylamino)-6-naphthylvinyl)pyridinium betaine