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: 105/4/1301    most recent 90414.2008v1 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 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 (2) Citing Articles via Google Scholar Google Scholar Articles by Johnson, S. M. Articles by Richerson, G. B. Search for Related Content PubMed PubMed Citation Articles by Johnson, S. M. Articles by Richerson, G. B.

GFP-expressing locus ceruleus neurons from Prp57 transgenic mice exhibit CO₂/H⁺ responses in primary cell culture

¹Department of Physiology and Biophysics, Howard University, College of Medicine, Washington, District of Columbia; ²Rainbow Babies and Children's Hospital, Developmental Neurobiology of Breathing and Airways Laboratories, Case Western Reserve University, Cleveland, Ohio; and ³Department of Neurology, Yale University School of Medicine, New Haven, Connecticut

Submitted 17 March 2008 ; accepted in final form 12 July 2008

The locus ceruleus (LC) contains neurons that increase their firing rate (FR) in vitro when exposed to elevated CO₂/H⁺ and have been proposed to influence the respiratory network to make compensatory adjustments in ventilation. Prp57 transgenic mice express green fluorescent protein (GFP) in the LC and were used to isolate, culture, and target LC neurons for electrophysiological recording. We hypothesized that GFP-LC neurons would exhibit CO₂/H⁺ chemosensitivity under primary culture conditions, evidenced as a change in FR. This is the first study to quantify CO₂/H⁺ responses in LC neuron FR in cell culture. Neurons were continuously bathed with solutions containing antagonists of glutamate and GABA receptors, and the acid-base status was changed from control (5% CO₂; pH 7.4) to hypercapnic acidosis (9% CO₂; pH 7.2) and hypocapnic alkalosis (3% CO₂; pH 7.6). FR was quantified during perforated patch current clamp recordings. Approximately 86% of GFP-LC neurons were stimulated, and 14% were insensitive to changes in CO₂/H⁺. The magnitude of the response of these neurons depended on the baseline FR, ranging from 155.9 ± 6% when FR started at 2.95 ± 0.49 Hz to 381 ± 55.6% when FR started at 1.32 ± 0.31 Hz. These results demonstrate that cultured LC neurons from Prp57 transgenic mice retain functional sensing molecules necessary for CO₂/H⁺ responses. Prp57 transgenic mice will serve as a valuable model to delineate mechanisms involved in CO₂/H⁺ responsiveness in catecholaminergic neurons.

CO₂/H⁺ chemosensitivity; central respiratory chemoreceptors; carbon dioxide; primary cell culture; pH response

This article has been cited by other articles:

				P. Taneja, M. Ogier, G. Brooks-Harris, D. A. Schmid, D. M. Katz, and S. B. Nelson Pathophysiology of Locus Ceruleus Neurons in a Mouse Model of Rett Syndrome J. Neurosci., September 30, 2009; 29(39): 12187 - 12195. [Abstract] [Full Text] [PDF]

				N. L. Nichols, D. K. Mulkey, K. A. Wilkinson, F. L. Powell, J. B. Dean, and R. W. Putnam Characterization of the chemosensitive response of individual solitary complex neurons from adult rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R763 - R773. [Abstract] [Full Text] [PDF]