Chronic High-Inspired CO₂ Decreases Excitability of Mouse Hippocampal Neurons

Abstract

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).

Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

“…*P Ͻ 0.05. seen (including the decrease in body weight) may result from a delay in development, we have evidence from our laboratory, although not for acid-base transporters, of enhancement of development and maturation with CO 2 exposure. For example, CO 2 enhances sodium channel maturation and excitability in early life (33,34), increases kidney size, and shows evidence of enhanced capillary-alveolar maturation (42). Changes in acid-base transporter expression and/or activity have been demonstrated in response to various acute and chronic stimuli that affect pH i , such as hypoxia, bicarbonate loading, metabolic acidosis, and alkalosis (4,23,26,27,40,48,69).…”

“…We hypothesized that, to maintain pH homeostasis during chronic CO 2 exposure, there will be an increase in the expression of acid extruders and/or a decrease in the expression of acid loaders and that the extent of change will most likely be greater in the neonate compared with the adult. Previously, our laboratory and others have shown that varying the level of CO 2 to which the animal is exposed, strongly influences the functional response as well as pattern of gene and/or protein expression in many organs including the brain, lung, and heart (33,38,42). Therefore, we exposed mice in this study to both a moderate (8% CO 2 ) and a severe (12% CO 2 ) hypercapnia and examined by immunoblot analysis the effect of chronically elevated CO 2 exposure on the membrane protein expression of the major acid-base transporter proteins in the brain, heart, and kidneys of neonatal and adult mice.…”

Respiratory gases and the regulation of transcription

“…Chronic long‐term exposure to elevated CO 2 also decreases neuronal excitability (Gu et al . ). Importantly, CO 2 impacts on mammalian cells on a transcriptional as well as a neuronal level (Li et al .…”

Time-dependent effect of acute hypoxia on corticospinal excitability in healthy humans

“…bonates (Bonnet et al 1998; Bruehl and Witte 2003;Gu et al 2000Gu et al , 2007. Some previous results(Ainslie et al 2007; Good- Mechanical and EMG quadriceps responses during maximal voluntary or evoked contractions as well as maximal peripheral and cortical voluntary activation levels in normoxia and after 1 h (Part 1) or 3 h (Part 2) of hypoxic breathingValues are means (SD).…”