QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Ai, X. Articles by Hall, A. K. Search for Related Content PubMed PubMed Citation Articles by Ai, X. Articles by Hall, A. K.

 Previous Article  |  Next Article 

The Journal of Neuroscience, November 15, 1998, 18(22):9294-9302

Depolarization Stimulates Initial Calcitonin Gene-Related Peptide Expression by Embryonic Sensory Neurons In Vitro

Xingbin Ai, Sally E. MacPhedran, and Alison K. Hall

Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106-4975

The neuropeptide calcitonin gene-related peptide (CGRP) is expressed by one-third of adult rat lumbar dorsal root ganglion (DRG) neurons, many of which mediate pain sensation or cause vasodilation. The factors that regulate the developmental expression of CGRP are poorly understood. Embryonic DRG neurons initially lack CGRP. When these neurons were stimulated in culture by serum or persistent 50 mM KCl application, the same percentage of CGRP-immunoreactive (CGRP-IR) neurons developed in vitro as was seen in the adult DRG in vivo. The addition of the L-type calcium channel blockers, 5 µM nifedipine or 10 µM verapamil, dramatically decreased the proportion of CGRP-IR neurons that developed, although the N-type calcium channel blocker, 2.5 µM -conotoxin, was less effective. By contrast, the sodium channel blocker 1 µM tetrodotoxin had no effect on CGRP expression after depolarization. Fura-2 ratiometric imaging demonstrated that mean intracellular free calcium levels increased from 70 to 135 nM with chronic depolarization, and the addition of nifedipine inhibited that increase. Only a subpopulation of neurons had elevated calcium concentrations during chronic depolarization, and they were correlated with CGRP expression. Key signal transduction pathways were tested pharmacologically for their role in CGRP expression after depolarization; the addition of the CaM kinase inhibitor KN-62 reduced the proportion of CGRP-IR neurons to basal levels. By contrast, protein kinase A and protein kinase C were not implicated in the depolarization-induced CGRP increases. These data suggest that depolarization and the subsequent Ca²⁺-based signal transduction mechanisms play important roles in the de novo expression of CGRP by specific embryonic DRG neurons.

Key words: sensory ganglion; calcitonin gene-related peptide; depolarization; signal transduction; ion channel; calcium imaging

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/18229294-09$05.00/0

This article has been cited by other articles:

				A. Grigaliunas, R. M. Bradley, D. K. MacCallum, and C. M. Mistretta Distinctive Neurophysiological Properties of Embryonic Trigeminal and Geniculate Neurons in Culture J Neurophysiol, October 1, 2002; 88(4): 2058 - 2074. [Abstract] [Full Text] [PDF]

				T. A. Brosenitsch and D. M. Katz Physiological Patterns of Electrical Stimulation Can Induce Neuronal Gene Expression by Activating N-Type Calcium Channels J. Neurosci., April 15, 2001; 21(8): 2571 - 2579. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help