Chronic high inspired CO 2 decreases excitability of mouse hippocampal neurons

Abstract

To examine the effect of chronically elevated CO2 on excitability and function of neurons, we exposed mice to 8% and 12% CO2 for 4 weeks (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). While 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), 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, II and 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 (Gu et al. 2004) 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. (This work was supported by NIH grants PO1 HD-32573, RO1 NS-35918 and RO1 HL-66327).