Article of the Month, October 2017 (Binshtok's lab)

October 15, 2017
Ultrafast optical recording reveals distinct capsaicin-induced ion dynamics along single nociceptive neurite terminals in vitro

Authors: Goldstein et al. (Alex Binshtok lab)
Published on July, 2017 in Journal of Biomedical Optics


Changes in intra-terminal calcium following focal application of capsaicin. Note, that the calcium signal starts focally at the tip of the  lower terminal then it spreads proximally and then strong calcium  signal is generated  about 20 um from the terminal which then rapidly spreads upward



Pain signals are detected by terminals of nociceptive peripheral fibers situated among the keratinocytes and epithelial cells throughout the body. Despite being key structures for detection and transmission of painful stimuli, little is known about the physiological and functional organization of terminals. This is mainly due to their minute size, rendering them at large inaccessible by conventional experimental approaches. In this paper, we reported the implementation of an ultrafast optical recording approach for studying cultured terminal-like structures. Using this approach, we were able, for the first time, to directly study noxious stimuli-induced spatial calcium and sodium dynamics in the nociceptor terminal, at a time resolution approaching that of action potentials. Using this approach, we have demonstrated that the capsaicin-induced calcium and sodium signals change as they propagate from the terminal and along the neurite such that signal initiation at the terminals differs in its amplitude, kinetics and dependence of voltage gated sodium channels from the signal propagating along the neurite. Our results suggest that the terminal-like structure is functionally composed of two distinctive zones. In a first zone calcium propagates passively, likely via capsaicin-activated Ca2+ permeable TRPV1 channels.  In a second zone, Ca2+ propagation likely depends on voltage gated Ca2+ channels activated by action potential mediated depolarization. Moreover, we propose this ultrafast optical recording approach as a model for studying sensory transduction and propagation by peripheral terminals, which may shed new light on the mechanisms underlying the processing of noxious information at the nociceptive terminals; forming a basis for studying pain mechanism in normal and pathological states. 



Full article at: https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-22/issue-07/076010/Ultrafast-optical-recording-reveals-distinct-capsaicin-induced-ion-dynamics-along/10.1117/1.JBO.22.7.076010.full?SSO=1