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Effects of chronically elevated CO 2 on excitability of mice hippocampal neurons
Author(s) -
Gu Xiang Q.,
Yao H.,
Haddad G.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a326-c
Subject(s) - hippocampal formation , chemistry , endocrinology , medicine , hippocampus
To examine the effects of chronically elevated level of CO 2 on excitability and function of neurons, we exposed mice to either 8% CO 2 or 12% CO 2 for 2 weeks (starting at 2–3 days of age), and examined the properties of freshly dissociated hippocampal neurons obtained from slices. As compared to control (CON) hippocampal CA1 neurons, chronic CO 2 treated neurons (CC) had similar input resistances (R m ). CC neurons, however, had a higher Na + current density (624 ± 98 pA/pF, n=19, 647 ± 94 pA/pF, n=46 for 8% and 12% CC respectively) than CON neurons (272 ± 53 pA/pF, n=30). Na + channel characteristics were also significantly altered by chronic CO 2 treatment. The steady state inactivation curve was not changed by 12% treatment but shifted in a more positive direction in 8% CC treatment as compared to CON (with a mid‐point of the curve −61 ± 2, n=16 and −67 ± 2, n=34 for 8% and 12% CC respectively and −67 ± 3 mV, n=19 for CON. The time constant for deactivation (τ d ) at −100 mV was also smaller in 8% CC than in CON (0.8 ± 0.2 ms, n=14 for CC and 2.0 ± 0.1 ms, n=17 for CON), but unchanged in 8%CC (1.7 ± 0.3 ms, n=34). We conclude that (1) the increased neuronal excitability in mice chronically treated with elevated CO 2 (8%) environment is due to alterations in Na + current and Na + channel characteristics; (2) that unchanged neuronal excitability in mice chronically treated with 12% CO 2 is also due to unchanged gating properties such as steady state inactivation and deactivation. We hypothesize from these and previous data from our laboratory that (a) this increased excitability in 8% CC environment reflects enhancement of central nervous system maturation when exposed to elevated CO 2 conditions in postnatal life; (2) neuronal excitability depends on the level of CO 2 exposure. (This work was supported by NIH grants P01 HD‐32573, R01 NS‐35918 and R01 HL‐66327).