HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 584/1/313    most recent jphysiol.2007.140624v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kuri, B. A. Articles by Smith, C. B. Search for Related Content PubMed PubMed Citation Articles by Kuri, B. A. Articles by Smith, C. B. Related Collections Integrative

¹ Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970, USA

Previous studies have shown that catecholamine secretion from the adrenal medulla plays a critical role in chronic intermittent hypoxia (CIH)-induced alterations in cardiovascular function. In the present study we examined the cellular mechanisms associated with the effects of CIH on adrenal chromaffin cell catecholamine secretion. Experiments were performed on adult male mice (C57/BL6) that were exposed to 1–4 days of CIH or to normoxia. Perforated patch electrical capacitance recordings were performed on freshly prepared adrenal medullary slices that permit separating the chromaffin cell secretion from sympathetic input. CIH resulted in a significant increase in the readily releasable pool (RRP) of secretory granules, and decreased stimulus-evoked Ca²⁺ influx. Continuous hypoxia (CH) either for 2.5 h (equivalent to hypoxic duration accumulated over 4 days of CIH) or for 4 days were ineffective in evoking changes in the RRP and Ca²⁺ influx. CIH activated PKC in adrenal medullae as evidenced by increased phosphorylation of PKC at Thr⁵¹⁴ and PKC inhibitors prevented CIH-induced increases in the RRP and restored stimulus-evoked attenuation of Ca²⁺ influx. CIH resulted in elevated thio-barbituric acid reactive substances (TBARSs, an index of oxidized proteins) and an antioxidant prevented CIH-induced changes in the RRP, suggesting the involvement of reactive oxygen species (ROS). These results demonstrate that CIH increases the RRP in adrenal chromaffin cells via ROS-mediated activation of PKC and suggest that CIH can directly affect the secretory capacity of chromaffin cells and contribute, in part, to elevated catecholamine levels.

(Received 12 July 2007; accepted after revision 3 August 2007; first published online 16 August 2007)
Corresponding author C. Smith: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970, USA. Email: corey.smith{at}case.edu