Maturation of neuronal excitability in hippocampal neurons of mice chronically exposed to cyclic hypoxia.

To examine the effects of chronic cyclic hypoxia on neuronal excitability and function in mice, we exposed mice to cyclic hypoxia for 8 h daily (9 cycles/h) for approximately 2 wk (starting at 2-3 days of age) and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Compared with control (Con) hippocampal CA1 neurons, exposed neurons (CYC) had similar resting membrane potentials (V(m)) and action potentials (AP). CYC neurons, however, had a lower rheobase than Con neurons. There was also an upregulation of the Na(+) current density (333 +/- 84 pA/pF, n = 18) in CYC compared with that of Con neurons (193 +/- 20 pA/pF, n = 27, P < 0.03). Na(+) channel characteristics were significantly altered by hypoxia. For example, the steady-state inactivation curve was significantly more positive in CYC than in Con (-60 +/- 6 mV, n = 8, for CYC and -71 +/- 3 mV, n = 14, for Con, P < 0.04). The time constant for deactivation (tau(d)) was much shorter in CYC than in Con (at -100 mV, tau(d)=0.83 +/- 0.23 ms in CYC neurons and 2.29 +/- 0.38 ms in Con neurons, P = 0.004). We conclude that the increased neuronal excitability in mice neurons treated with cyclic hypoxia is due to alterations in Na(+) channel characteristics and/or Na(+) channel expression. We hypothesize from these and previous data from our laboratory (Gu XQ and Haddad GG. J Appl Physiol 91: 1245-1250, 2001) that this increased excitability is a reflection of an enhanced central nervous system maturation when exposed to low O(2) conditions in early postnatal life.