Effects of chronically elevated CO 2 on excitability of mice hippocampal neurons

Abstract

To examine the effects of chronically elevated level of CO2 on excitability and function of neurons, we exposed mice to either 8% CO2 or 12% CO2 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 CO2 treated neurons (CC) had similar input resistances (Rm). 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 CO2 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 (τd) 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 CO2 (8%) environment is due to alterations in Na+ current and Na+ channel characteristics; (2) that unchanged neuronal excitability in mice chronically treated with 12% CO2 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 CO2 conditions in postnatal life; (2) neuronal excitability depends on the level of CO2 exposure. (This work was supported by NIH grants P01 HD-32573, R01 NS-35918 and R01 HL-66327).