Decreased neuronal excitability in hippocampal neurons of mice exposed to cyclic
hypoxia.
Gu, Xiang Q., and Gabriel G. Haddad.
Departments of 1Pediatrics (Section of Respiratory Medicine) and 2Cellular and
Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut
06510
APStracts 8:0271A, 2001.
To study the physiological effects of chronic intermittent hypoxia on neuronal
excitability and function in mice, we exposed animals to cyclic hypoxia for 8 h daily (12
cycles/h) for ~4 wk, starting at 2-3 days of age, and examined the properties of freshly
dissociated hippocampal neurons in vitro. Compared with control (Con) hippocampal
CA1 neurons, exposed (Cyc) neurons showed action potentials (AP) with a smaller
amplitude and a longer duration and a more depolarized resting membrane potential.
They also have a lower rate of spontaneous firing of AP and a higher rheobase.
Furthermore, there was downregulation of the Na+ current density in Cyc compared with
Con neurons (356.09 ± 54.03 pA/pF in Cyc neurons vs. 508.48 ± 67.30 pA/pF in Con, P
< 0.04). Na+ channel characteristics, including activation, steady-state inactivation, and
recovery from inactivation, were similar in both groups. The deactivation rate, however,
was much larger in Cyc than in Con (at «minus»100 mV, time constant for deactivation =
0.37 ± 0.04 ms in Cyc neurons 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 membrane potential) and in
Na+ channel expression and/or regulation. We hypothesize 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 O2 conditions.
Received 14 February 2001; accepted in final form 19 April 2001
APS Manuscript Number A0154-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 18 June 2001