Effect of chronically elevated CO2 on CA1 neuronal excitability.
To study the effect of chronically elevated CO(2) on the excitability and function of neurons, we exposed mice to 7.5-8% CO(2) for approximately 2 wk (starting at 2 days of age) and examined the properties of freshly dissociated hippocampal neurons. Neurons from control mice (CON) and from mice exposed to chronically elevated CO(2) had similar resting membrane potentials and input resistances. CO(2)-exposed neurons, however, had a lower rheobase and a higher Na(+) current density (580 +/- 73 pA/pF; n = 27 neurons studied) than did CON neurons (280 +/- 51 pA/pF, n = 34; P < 0.01). In addition, the conductance-voltage curve was shifted in a more negative direction in CO(2)-exposed than in CON neurons (midpoint of the curve was -46 +/- 3 mV for CO(2) exposed and -34 +/- 3 mV for CON, P < 0.01), while the steady-state inactivation curve was shifted in a more positive direction in CO(2)-exposed than in CON neurons (midpoint of the curve was -59 +/- 2 mV for CO(2) exposed and -68 +/- 3 mV for CON, P < 0.01). The time constant for deactivation at -100 mV was much smaller in CO(2)-exposed than in CON neurons (0.8 +/- 0.1 ms for CO(2) exposed and 1.9 +/- 0.3 ms for CON, P < 0.01). Immunoblotting for Na(+) channel proteins (subtypes I, II, and III) was performed on the hippocampus. Our data indicate that Na(+) channel subtype I, rather than subtype II or III, was significantly increased (43%, n = 4; P < 0.05) in the hippocampi of CO(2)-exposed mice. We conclude that in mice exposed to elevated CO(2), 1) increased neuronal excitability is due to alterations in Na(+) current and Na(+) channel characteristics, and 2) the upregulation of Na(+) channel subtype I contributes, at least in part, to the increase in Na(+) current density.
Gu
Xiang Q
XQ
Dept. of Pediatrics, Albert Einstein College of Medicine, Rose F. Kennedy Center for Research in Mental Retardation and Human Development, 1410 Pelham Parkway South, Bronx, NY 10461, USA.
Xue
Jin
J
Haddad
Gabriel G
GG
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002478:Cells, Cultured; D004594:Electrophysiology; D006935:Hypercapnia / Q000503:physiopathology*; D015151:Immunoblotting; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
D015222:Sodium Channels; D002245:Carbon Dioxide