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J Neurophysiol 97: 1833-1838, 2007. First published January 3, 2007; doi:10.1152/jn.01174.2006 Free Article
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Chronic High-Inspired CO2 Decreases Excitability of Mouse Hippocampal Neurons

Xiang Q. Gu1, Amjad Kanaan1, Hang Yao1 and Gabriel G. Haddad1,2,3

1Departments of Pediatrics, Section of Respiratory Medicine and 2Neuroscience, University of California; and 3The Rady's Children's Hospital, San Diego, California

Submitted 3 November 2006; accepted in final form 28 December 2006

To examine the effect of chronically elevated CO2 on excitability and function of neurons, we exposed mice to 8 and 12% CO2 for 4 wk (starting at 2 days of age), and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Chronic CO2-treated neurons (CC) had a similar input resistance (Rm) and resting membrane potential (Vm) as control (CON). Although treatment with 8% CO2 did not change the rheobase (64 ± 11 pA, n = 9 vs. 47 ± 12 pA, n = 8 for CC 8% vs. CON; means ± SE), 12% CO2 treatment increased it significantly (73 ± 8 pA, n = 9, P = 0.05). Furthermore, the 12% CO2 but not the 8% CO2 treatment decreased the Na+ channel current density (244 ± 36 pA/pF, n = 17, vs. 436 ± 56 pA/pF, n = 18, for CC vs. CON, P = 0.005). Recovery from inactivation was also lowered by 12% but not 8% CO2. Other gating properties of Na+ current, such as voltage-conductance curve, steady-state inactivation, and time constant for deactivation, were not modified by either treatment. Western blot analysis showed that the expression of Na+ channel types I–III was not changed by 8% CO2 treatment, but their expression was significantly decreased by 20–30% (P = 0.03) by the 12% treatment. We conclude from these data and others that neuronal excitability and Na+ channel expression depend on the duration and level of CO2 exposure and maturational changes occur in early life regarding neuronal responsiveness to CO2.


Address for reprint requests and other correspondence: G. G. Haddad, Dept. of Pediatrics, University of California San Diego, 9500 Gilman Dr., San Diego, CA 92093-0735 (E-mail: ghaddad{at}ucsd.edu)




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A. Kanaan, R. M. Douglas, S. L. Alper, W. F. Boron, and G. G. Haddad
Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1294 - R1302.
[Abstract] [Full Text] [PDF]




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