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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Park, Hae Jeong Rajbhandari, Ira Yang, Han Soo Lee, Soojung Cucoranu, Delia Cooper, Deborah S. Klein, Janet D. Sands, Jeff M. Choi, Inyeong |
Description | Country affiliation: United States Author Affiliation: Park HJ ( Dept. of Physiology, Emory Univ., Atlanta, GA 30322, USA.) |
Abstract | The sodium-bicarbonate cotransporter NBCn1 (SLC4A7) is an acid-base transporter that normally moves Na(+) and HCO(3)(-) into the cell. This membrane protein is sensitive to cellular and systemic pH changes. We examined NBCn1 expression and localization in the brain and its response to chronic metabolic acidosis. Two new NBCn1 antibodies were generated by immunizing a rabbit and a guinea pig. The antibodies stained neurons in a variety of rat brain regions, including hippocampal pyramidal neurons, dentate gyrus granular neurons, posterior cortical neurons, and cerebellar Purkinje neurons. Choroid plexus epithelia were also stained. Double immunofluorescence labeling showed that NBCn1 and the postsynaptic density protein PSD-95 were found in the same hippocampal CA3 neurons and partially colocalized in dendrites. PSD-95 was pulled down from rat brain lysates with the GST/NBCn1 fusion protein and was also coimmunoprecipitated with NBCn1. Chronic metabolic acidosis was induced by feeding rats with normal chow or 0.4 M HCl-containing chow for 7 days. Real-time PCR and immunoblot showed upregulation of NBCn1 mRNA and protein in the hippocampus of acidotic rats. NBCn1 immunostaining was enhanced in CA3 neurons, posterior cortical neurons, and cerebellar granular cells. Intraperitoneal administration of N-methyl-d-aspartate caused neuronal death determined by caspase-3 activity, and this effect was more severe in acidotic rats. Administering N-methyl-d-aspartate also inhibited NBCn1 upregulation in acidotic rats. We conclude that NBCn1 in neurons is upregulated by chronic acid loads, and this upregulation is associated with glutamate excitotoxicity. |
File Format | HTM / HTML |
ISSN | 03636143 |
e-ISSN | 15221563 |
DOI | 10.1152/ajpcell.00492.2009 |
Journal | American Journal of Physiology - Cell Physiology |
Issue Number | 5 |
Volume Number | 298 |
Language | English |
Publisher | American Physiological Society |
Publisher Date | 2010-05-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Discipline Cell Biology Acidosis Metabolism Neurons Sodium-bicarbonate Symporters Blood Chemically Induced Urine Animals Antibodies Bicarbonates Caspase 3 Cell Death Gene Expression Regulation Guinea Pigs Hippocampus Cytology Hydrogen-ion Concentration Rna, Messenger Genetics Rabbits Rats, Sprague-dawley Chemistry Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
Content Type | Text |
Resource Type | Article |
Subject | Physiology Cell Biology |
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