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

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 96/3/1206    most recent 00879.2003v1 Submit a response 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 (12) Citing Articles via Google Scholar Google Scholar Articles by Kim, D.-K. Articles by Kumar, G. K. Search for Related Content PubMed PubMed Citation Articles by Kim, D.-K. Articles by Kumar, G. K.

HIGHLIGHTED TOPICS
Oxygen Sensing in Health and Disease

Facilitation of dopamine and acetylcholine release by intermittent hypoxia in PC12 cells: involvement of calcium and reactive oxygen species

¹Department of Biochemistry, and ²Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106

Submitted 19 August 2003 ; accepted in final form 24 November 2003

We have investigated the effects of preconditioning pheochromocytoma (PC12) cells with intermittent hypoxia (IH) on transmitter release during acute hypoxia. Cell cultures were exposed to either alternating cycles of hypoxia (1% O₂ + 5% CO₂; 30 s/cycle) and normoxia (21% O₂ + 5% CO₂; 3 min/cycle) for 15 or 60 cycles or normoxia alone (control) for similar durations. Control and IH cells were challenged with either hyperoxia (basal release) or acute hypoxia (PO₂ of 35 Torr) for 5 min, and the amounts of dopamine (DA) and acetylcholine (ACh) released in the medium were determined by HPLC combined with electrochemical detection. Hypoxia augmented DA (80%) but not ACh release in naive cells, whereas, in IH-conditioned cells, it further enhanced DA release (ranging from 120 to 145%) and facilitated ACh release (30%). Hypoxia-evoked augmentation of transmitter release was not seen in cells conditioned with sustained hypoxia. IH-induced increase in DA but not IH-induced ACh release during hypoxia was partially inhibited by cadmium chloride (100 µM), a voltage-gated Ca²⁺ channel blocker. By contrast, 2-aminoethoxydiphenylborate (75 µM), a blocker of inositol 1,4,5-trisphosphate (IP₃) receptors, and N-acetyl-L-cysteine (300 µM), a potent scavenger of reactive oxygen species, either attenuated or abolished IH-evoked augmentation of transmitter release during hypoxia. Together, the above results demonstrate that IH conditioning increases hypoxia-evoked neurotransmitter release from PC12 cells via mechanisms involving mobilization of Ca²⁺ from intracellular stores through activation of IP₃ receptors. Our findings also suggest that oxidative stress plays a central role in IH-induced augmentation of transmitter release from PC12 cells during acute hypoxia.

intracellular calcium mobilization; inositol 1,4,5-trisphosphate receptors

This article has been cited by other articles:

				S. Rey, J. Corthorn, C. Chacon, and R. Iturriaga Expression and Immunolocalization of Endothelin Peptides and Its Receptors, ETA and ETB, in the Carotid Body Exposed to Chronic Intermittent Hypoxia J. Histochem. Cytochem., February 1, 2007; 55(2): 167 - 174. [Abstract] [Full Text] [PDF]

				Y.-J. Peng, G. Yuan, D. Ramakrishnan, S. D. Sharma, M. Bosch-Marce, G. K. Kumar, G. L. Semenza, and N. R. Prabhakar Heterozygous HIF-1{alpha} deficiency impairs carotid body-mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia J. Physiol., December 1, 2006; 577(2): 705 - 716. [Abstract] [Full Text] [PDF]

				G. K. Kumar, V. Rai, S. D. Sharma, D. P. Ramakrishnan, Y.-J. Peng, D. Souvannakitti, and N. R. Prabhakar Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress J. Physiol., August 15, 2006; 575(1): 229 - 239. [Abstract] [Full Text] [PDF]

				G. C. Sieck Commentary J Appl Physiol, March 1, 2004; 96(3): 1196 - 1196. [Full Text] [PDF]