Decreased neuronal excitability in hippocampal neurons of mice exposed to cyclic hypoxia

To study the physiological effects of chronic intermittent hypoxia on neuro nal excitability and function in mice, we exposed animals to cyclic hypoxia for 8 h daily (12 cycles/h) for similar to4 wk, starting at 2-3 days of ag e, and examined the properties of freshly dissociated hippocampal neurons i n vitro. Compared with control (Con) hippocampal CA1 neurons, exposed (Cyc) neurons showed action potentials (AP) with a smaller amplitude and a longe r duration and a more depolarized resting membrane potential. They also hav e a lower rate of spontaneous firing of AP and a higher rheobase. Furthermo re, there was downregulation of the Na+ current density in Cyc compared wit h Con neurons (356.09 +/- 54.03 pA/pF in Cyc neurons vs. 508.48 +/- 67.30 p A/pF in Con, P< 0.04). Na+ channel characteristics, including activation, s teady-state inactivation, and recovery from inactivation, were similar in b oth groups. The deactivation rate, however, was much larger in Cyc than in Con (at -100 mV, time constant for deactivation = 0.37 +/- 0.04 ms in Cyc n eurons and 0.18 +/- 0.01 ms in Con neurons). We conclude that the decreased neuronal excitability in mice neurons treated with cyclic hypoxia is due, at least in part, to differences in passive properties (e.g., resting membr ane potential) and in Na+ channel expression and/or regulation. We hypothes ize that this decreased excitability is an adaptive response that attempts to decrease the energy expenditure that is used for adjusting disturbances in ionic homeostasis in low-O-2 conditions.