Journal article
Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a
Proceedings of the National Academy of Sciences - PNAS, Vol.101(17), pp.6752-6757
04/27/2004
DOI: 10.1073/pnas.0308636100
PMCID: PMC404117
PMID: 15082829
Abstract
Acid-sensing ion channel (ASIC) 1a subunit is expressed in synapses of central neurons where it contributes to synaptic plasticity. However, whether these channels can conduct Ca
2+
and thereby raise the cytosolic Ca
2+
concentration, [Ca
2+
]
c
, and possibly alter neuronal physiology has been uncertain. We found that extracellular acidosis opened ASIC1a channels, which provided a pathway for Ca
2+
entry and elevated [Ca
2+
]
c
in wild-type, but not ASIC1
-/-
, hippocampal neurons. Acid application also raised [Ca
2+
]
c
and evoked Ca
2+
currents in heterologous cells expressing ASIC1a. Although ASIC2a is also expressed in central neurons, neither ASIC2a homomultimeric channels nor ASIC1a/2a heteromultimers showed H
+
-activated [Ca
2+
]
c
elevation or Ca
2+
currents. Because extracellular acidosis accompanying cerebral ischemia contributes to neuronal injury, we tested the effect of acidosis on cell death measured as lactate dehydrogenase release. Eliminating ASIC1a from neurons or treating ASIC1a-expressing cells with the ASIC blocker amiloride attenuated acidosis-induced cell injury. These results indicate that ASIC1a provides a non-voltage-gated pathway for Ca
2+
to enter neurons. Thus, it may provide a target for modulation of [Ca
2+
]
c
.
Details
- Title: Subtitle
- Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a
- Creators
- Olena Yermolaieva - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242A. Soren Leonard - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Mikael K Schnizler - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Francois M Abboud - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Michael J Welsh - Departments of Internal Medicine and Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.101(17), pp.6752-6757
- DOI
- 10.1073/pnas.0308636100
- PMID
- 15082829
- PMCID
- PMC404117
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 04/27/2004
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984013117802771
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