PT  - JOURNAL ARTICLE
AU  - Gover, Tony D.
AU  - Kao, Joseph P. Y.
AU  - Weinreich, Daniel
TI  - Calcium Signaling in Single Peripheral Sensory Nerve Terminals
AID  - 10.1523/JNEUROSCI.23-12-04793.2003
DP  - 2003 Jun 15
TA  - The Journal of Neuroscience
PG  - 4793--4797
VI  - 23
IP  - 12
4099  - http://www.jneurosci.org/content/23/12/4793.short
4100  - http://www.jneurosci.org/content/23/12/4793.full
SO  - J. Neurosci.2003 Jun 15; 23
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).