Calcium signaling in single peripheral sensory nerve terminals.
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 microm saxitoxin (STX), or L-type Ca2+ channel antagonists (1 mm diltiazem or 20 microm nifedipine). The nociceptive agonist capsaicin (1 microm) elicited Ca2+ transients in all nerve terminals studied. Capsaicin-evoked Ca2+ transients were completely blocked by the vanilloid receptor 1 antagonist capsazepine (100 microm). In contrast, capsaicin-evoked Ca2+ transients were not attenuated by preincubation with 4.1 microm STX or 20 microm nifedipine. These findings demonstrate, for the first time, that nerve impulses or chemical stimulation promote Ca2+ entry into PSNTs, including nociceptors.
Gover
Tony D
TD
The Neuroscience Program, University of Maryland, Baltimore, Maryland 21201-1559, USA.
Kao
Joseph P Y
JP
Weinreich
Daniel
D
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003315:Cornea / Q000294:innervation; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013268:Stimulation, Chemical
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D026941:Sodium Channel Blockers; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium