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Review
. 2009 Nov-Dec;13(11-12):4304-18.
doi: 10.1111/j.1582-4934.2009.00952.x. Epub 2009 Oct 23.

Sensing, physiological effects and molecular response to elevated CO2 levels in eukaryotes

Kfir Sharabi  1 , Emilia Lecuona, Iiro Taneli Helenius, Greg J Beitel, Jacob Iasha Sznajder, Yosef Gruenbaum
Affiliations
Review

Sensing, physiological effects and molecular response to elevated CO2 levels in eukaryotes

Kfir Sharabi et al. J Cell Mol Med. 2009 Nov-Dec.

Abstract

Carbon dioxide (CO(2)) is an important gaseous molecule that maintains biosphere homeostasis and is an important cellular signalling molecule in all organisms. The transport of CO(2) through membranes has fundamental roles in most basic aspects of life in both plants and animals. There is a growing interest in understanding how CO(2) is transported into cells, how it is sensed by neurons and other cell types and in understanding the physiological and molecular consequences of elevated CO(2) levels (hypercapnia) at the cell and organism levels. Human pulmonary diseases and model organisms such as fungi, C. elegans, Drosophila and mice have been proven to be important in understanding of the mechanisms of CO(2) sensing and response.

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Figures

Figure 3
Figure 3
Schematic model of the pathway leading to hypercapnia-induced Na,K-ATPase endocytosis in alveolar epithelial cells. Elevated CO2 levels initiate an intracellular Ca2+-dependent signalling pathway that involves the activation of CaMKK-β, AMPK and PKC-ζ, which in turns phosphorylates the Na,K-ATPase α1-subunit at Ser18, triggering its endocytosis and thus impairing AFR, an essential function of the alveolar epithelium.
Figure 1
Figure 1
Growth in air containing 19% CO2 reduces motility and affects muscle morphology in C. elegans. (A) The average number of head movements of wild-type (N2) animals at the L4 larval stage grown in air or in air containing 19% CO2 on agar plates or in a water drop. All measurements were performed after the animals were removed from the CO2 chamber. The number of head movements/minute was divided by the average number of head movement of animals grown in air. (B) Thin-section electron micrographs demonstrating the gradual deterioration of body muscles in animals grown for 4, 8 or 12 days in air containing 19% CO2 at 20°C. Muscle morphology was normal in animals grown in air. The muscle of animals grown in air containing 19% CO2 had deteriorated already at day 4 and muscle filaments were further disorganized at days 8 and 12. Scale bars = 500 nm. The data were taken from Ref. [18].
Figure 2
Figure 2
Schematic model of the pathway leading to hypercapnia-induced activation of L-type Ca2+ channels in carotid neurons. Elevated CO2 levels are converted by CA to protons and HCO3−. The carbonate directly activates the expression of sAC, which converts ATP to cyclic AMP (cAMP). The cAMP activates PKA, which is believed to activate the L-type Ca2+ channels leading to Ca2+ entry into cells. This model is based on a model proposed in [22].
Figure 4
Figure 4
Schematic model of the pathway leading to CO2 avoidance in C. elegans CO2 avoidance is mediated by the cGMP signalling pathway molecules TAX-2 and TAX-4 expression in the BAG neurons. The avoidance behaviour is also modulated by the neuropeptide Y receptor NPR-1, by the neuronal globin domain protein GLB-5, and by the insulin and TGF-β starvation pathways.
Figure 5
Figure 5
Hypercapnia induces change in gene expression in C. elegans. Fold change in log2 scale of gene expression during 1, 6 or 72 hrs exposure to air containing 19% CO2 of innate immunity (A), heat shock (B), 7-transmembrane domain (C), major sperm proteins (D), nuclear hormone receptor (E) and several other genes of interest. The data were taken from [18].
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