title: Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling.
abstract: Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses.
authors.affiliation: Department of Biomedical Engineering, University of Miami, Miami, Florida; and.
authors.forename: Vicente
authors.initials: V
authors.lastname: Lumbreras
authors.affiliation: Department of Otolaryngology, University of Miami, Miami, Florida.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Bas
authors.affiliation: Department of Otolaryngology, University of Miami, Miami, Florida.
authors.forename: Chhavi
authors.initials: C
authors.lastname: Gupta
authors.affiliation: Department of Biomedical Engineering, University of Miami, Miami, Florida; and Department of Otolaryngology, University of Miami, Miami, Florida s.rajguru@miami.edu.
authors.forename: Suhrud M
authors.initials: SM
authors.lastname: Rajguru
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000528:radiation effects*; D002478:Cells, Cultured; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007259:Infrared Rays; D008928:Mitochondria / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013136:Spiral Ganglion / Q000166:cytology / Q000528:radiation effects*; D013696:Temperature; D013841:Thiazepines / Q000494:pharmacology; D014725:Vestibular Nerve / Q000166:cytology / Q000528:radiation effects*
chemical_list: D002121:Calcium Channel Blockers; D007211:Indoles; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D013841:Thiazepines; D012430:Ruthenium Red; D012433:Ryanodine; D002998:Clonazepam; C079032:CGP 37157; C000543:cyclopiazonic acid
keywords: calcium photocontrol; cochlear implants; infrared radiation; mitochondria; neuroprostheses; optical stimulation; vestibular