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Am J Physiol Cell Physiol 289: C1122-C1133, 2005. First published June 1, 2005; doi:10.1152/ajpcell.00514.2004
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Maintenance of quantal size and immediately releasable granules in rat chromaffin cells by glucocorticoid

Jianhua Xu,1,2,* Kim San Tang,1,* Van B. Lu,1 Chandana P. Weerasinghe,1 Amy Tse,1,2 and Frederick W. Tse1,2

1Department of Pharmacology and 2Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada

Submitted 22 October 2004 ; accepted in final form 26 May 2005

Glucocorticoid is reported to regulate catecholamine synthesis and storage. However, it is not clear whether the actual amount of catecholamine released from individual granules (quantal size, Q) in mature chromaffin cells is affected by glucocorticoid. Using carbon fiber amperometry, we found that dexamethasone did not affect mean cellular Q or the proportional release from different populations of granules in rat chromaffin cells cultured for 1 day in a serum-free defined medium. After two extra days of culture in the defined medium, there was a rundown in mean cellular Q, and it was associated with a shift in the proportional release from the different granule populations. This phenomenon could not be rescued by serum supplementation but could be prevented by dexamethasone via an action that was independent of changes in voltage-gated Ca2+ channel (VGCC) density. Using simultaneous measurements of membrane capacitance and cytosolic Ca2+ concentration, we found that for cells cultured in defined medium dexamethasone enhanced the exocytotic response triggered by a brief depolarization (50 ms) without affecting the VGCC density or the fast exocytotic response triggered via flash photolysis of caged Ca2+. Thus glucocorticoid may regulate the number of immediately releasable granules that are in close proximity to a subset of VGCC. Because chromaffin cells in vivo are exposed to high concentrations of glucocorticoid, our findings suggest that the paracrine actions of glucocorticoid maintain the mean catecholamine content in chromaffin cell granules as well as the colocalization of releasable granules with VGCCs.

catecholamines; paracrine action; exocytosis; calcium channels



Address for reprint requests and other correspondence: F. W. Tse, Dept. of Pharmacology, 9-70 Medical Sciences Bldg., Univ. of Alberta, Edmonton, AB, T6G 2H7, Canada (e-mail: fred.tse{at}ualberta.ca)







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