Chronic high-inspired CO2 decreases excitability of mouse hippocampal neurons.
To examine the effect of chronically elevated CO(2) on excitability and function of neurons, we exposed mice to 8 and 12% CO(2) for 4 wk (starting at 2 days of age), and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Chronic CO(2)-treated neurons (CC) had a similar input resistance (R(m)) and resting membrane potential (V(m)) as control (CON). Although treatment with 8% CO(2) did not change the rheobase (64 +/- 11 pA, n = 9 vs. 47 +/- 12 pA, n = 8 for CC 8% vs. CON; means +/- SE), 12% CO(2) treatment increased it significantly (73 +/- 8 pA, n = 9, P = 0.05). Furthermore, the 12% CO(2) but not the 8% CO(2) 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% CO(2). 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-III was not changed by 8% CO(2) treatment, but their expression was significantly decreased by 20-30% (P = 0.03) by the 12% treatment. We conclude from these data and others that neuronal excitability and Na(+) channel expression depend on the duration and level of CO(2) exposure and maturational changes occur in early life regarding neuronal responsiveness to CO(2).
Gu
Xiang Q
XQ
Department of Pediatrics, University of California-San Diego, 9500 Gilman Drive, San Diego, CA 92093-0735, USA.
Kanaan
Amjad
A
Yao
Hang
H
Haddad
Gabriel G
GG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D015153:Blotting, Western; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D002908:Chronic Disease; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D006935:Hypercapnia / Q000473:pathology / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
D015222:Sodium Channels; D002245:Carbon Dioxide