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Effect of chronically elevated CO2 on CA1 neuronal excitability
Xiang Q Gu1, Jin Xue, Gabriel G Haddad
1Dept. of Pediatrics, Albert Einstein College of Medicine, Rose F. Kennedy Center for Research in Mental Retardation and Human Development, 1410 Pelham Parkway South, Bronx, NY 10461, USA.
American Journal of Physiology. Cell Physiology
|April 30, 2004
Summary
Chronic high carbon dioxide (CO2) exposure increases neuronal excitability in mice by altering sodium (Na+) channel function. Specifically, elevated CO2 upregulates Na+ channel subtype I, enhancing Na+ current density in hippocampal neurons.
Area of Science:
- Neuroscience
- Physiology
- Biochemistry
Background:
- Chronic exposure to elevated carbon dioxide (CO2) can significantly impact physiological processes.
- Understanding the effects of hypercapnia on neuronal function is crucial for various medical conditions.
Purpose of the Study:
- To investigate the impact of sustained high CO2 levels on the excitability and function of hippocampal neurons in mice.
- To identify the specific molecular mechanisms, particularly involving sodium (Na+) channels, underlying these changes.
Main Methods:
- Mice were exposed to 7.5-8% CO2 for two weeks, starting in early development.
- Electrophysiological properties of dissociated hippocampal neurons were analyzed, including resting membrane potential, input resistance, rheobase, and Na+ current density.
- Voltage-dependence of Na+ channel gating (conductance-voltage and inactivation curves) and deactivation kinetics were examined.
- Immunoblotting was used to quantify Na+ channel protein subtypes (I, II, and III) in hippocampal tissue.
Main Results:
- CO2-exposed neurons exhibited increased Na+ current density and a lower rheobase compared to control neurons.
- The voltage-dependence of Na+ channel activation and inactivation was significantly altered in CO2-exposed neurons.
- The time constant for Na+ channel deactivation was reduced in neurons from CO2-exposed mice.
- Hippocampal tissue from CO2-exposed mice showed a significant increase in Na+ channel subtype I protein levels, but not subtypes II or III.
Conclusions:
- Chronic elevated CO2 exposure leads to increased neuronal excitability in mice.
- These changes in excitability are primarily driven by alterations in Na+ current and Na+ channel characteristics.
- Upregulation of Na+ channel subtype I is a key contributor to the increased Na+ current density observed under chronic hypercapnia.