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The Journal of Neuroscience, May 15, 2003, 23(10):4054-4065

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Lighting up the Senses: FM1-43 Loading of Sensory Cells through Nonselective Ion Channels

Jason R. Meyers,^1 * Richard B. MacDonald,^3 * Anne Duggan,^5,6 David Lenzi,² David G. Standaert,^4,7 Jeffrey T. Corwin,² and David P. Corey^5,6

¹Neuroscience Graduate Program and ²Departments of Otolaryngology-Head and Neck Surgery and Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, ³Program in Speech and Hearing Sciences, Health Sciences and Technology Program, Massachusetts Institute of Technology, Boston, Massachusetts 02139, ⁴Departments of Neurology and, ⁵Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, and Howard Hughes Medical Institute, ⁶Neurosurgery Service, and ⁷Neurology Service, Massachusetts General Hospital, Boston, Massachusetts 02114

We describe a novel mechanism for vital fluorescent dye entry into sensory cells and neurons: permeation through ion channels. In addition to the slow conventional uptake of styryl dyes by endocytosis, small styryl dyes such as FM1-43 rapidly and specifically label hair cells in the inner ear by entering through open mechanotransduction channels. This labeling can be blocked by pharmacological or mechanical closing of the channels. This phenomenon is not limited to hair cell transduction channels, because human embryonic kidney 293T cells expressing the vanilloid receptor (TRPV1) or a purinergic receptor (P2X₂) rapidly take up FM1-43 when those receptor channels are opened and not when they are pharmacologically blocked. This channel permeation mechanism can also be used to label many sensory cell types in vivo. A single subcutaneous injection of FM1-43 (3 mg/kg body weight) in mice brightly labels hair cells, Merkel cells, muscle spindles, taste buds, enteric neurons, and primary sensory neurons within the cranial and dorsal root ganglia, persisting for several weeks. The pattern of labeling is specific; nonsensory cells and neurons remain unlabeled. The labeling of the sensory neurons requires dye entry through the sensory terminal, consistent with permeation through the sensory channels. This suggests that organic cationic dyes are able to pass through a number of different sensory channels. The bright and specific labeling with styryl dyes provides a novel way to study sensory cells and neurons in vivo and in vitro, and it offers new opportunities for visually assaying sensory channel function.

Key words: FM1-43; hair cell; vanilloid receptor; purinergic receptor; Merkel cells; DRG; nociceptors; TRP channels; sensory ganglia

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Received Jan. 2, 2003; revised Mar. 4, 2003; accepted Mar. 7, 2003.

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