RT Journal Article SR Electronic T1 Calcium Signaling in Single Peripheral Sensory Nerve Terminals JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4793 OP 4797 DO 10.1523/JNEUROSCI.23-12-04793.2003 VO 23 IS 12 A1 Gover, Tony D. A1 Kao, Joseph P. Y. A1 Weinreich, Daniel YR 2003 UL http://www.jneurosci.org/content/23/12/4793.abstract AB Peripheral sensory nerve terminals (PSNTs) have a dual function: reporting normal and abnormal sensations and releasing trophic factors to maintain the structure and function of epithelial cells. Although it is widely considered that intracellular Ca2+ plays a critical signaling role for both functions, the role of Ca2+ signaling has never been studied in PSNTs, primarily because of their small size and anatomical inaccessibility. Here, using epifluoresence microscopy and a fluorescent Ca2+ indicator, we report that action potentials or chemical irritation can elicit transient rises in [Ca2+]i (Ca2+ transients) in PSNTs within the corneal epithelium of the rat. In vitro electrical stimulation of the ciliary nerves in the eye, or electrical field stimulation of the cornea, evoked Ca2+ transients with a magnitude that was proportional to the number of stimuli applied over the range of 1–10 stimuli. Ca2+ transients were significantly blocked by 1 mm lidocaine, 4.1 μm saxitoxin (STX), or L-type Ca2+ channel antagonists (1 mm diltiazem or 20 μm nifedipine). The nociceptive agonist capsaicin (1 μm) elicited Ca2+ transients in all nerve terminals studied. Capsaicin-evoked Ca2+ transients were completely blocked by the vanilloid receptor 1 antagonist capsazepine (100 μm). In contrast, capsaicin-evoked Ca2+ transients were not attenuated by preincubation with 4.1 μm STX or 20 μm nifedipine. These findings demonstrate, for the first time, that nerve impulses or chemical stimulation promote Ca2+ entry into PSNTs, including nociceptors.Figure 1. Illustration of the branching pattern of Aδ and C fiber nerve terminals within the cornea. Aδ and C fibers course together in the collagenous stromal layer. The nerve plexus in the stromal layer consists of extensively branching Aδ and C fibers. The fibers separate as they turn toward the superficial epithelial layers, where they terminate. Letters in parentheses correspond to the images in Figure 2. Adapted from MacIver and Tanelian (1993).