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"The exciting implication of our study is that carbon dioxide is much more than just a waste product: it can directly signal physiological information, and our work shows the mechanism by which this happens via Connexin 26," says Nick Dale. (Credit: Tim Green/Flickr)

carbon dioxide

Signaling shows carbon dioxide isn’t just waste

Carbon dioxide isn’t just a metabolic waste product—it’s a biological signaling molecule, too, according to new research.

Researchers have shown that the body senses carbon dioxide directly through the protein Connexin 26, which acts as a receptor for the gas. Connexin 26 is better known as forming a direct channel of communication between cells. This new work shows an unexpected function for Connexin 26—as a receptor for carbon dioxide.

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This finding therefore adds carbon dioxide to the list of gaseous signaling molecules, such as nitric oxide, carbon monoxide, and hydrogen sulphide already known to be active in mammals.

“As Connexin 26 is present in many tissues and organs, for example the brain, skin, inner ear, liver, and the uterus during pregnancy, this discovery should herald a re-evaluation of the potential for carbon dioxide signaling in many different processes such as the control of blood flow, breathing, hearing, reproduction, and birth,” says Professor Nick Dale of the University of Warwick.

Carbon dioxide is the by-product of metabolism in all cells. Dissolved carbon dioxide can combine with water to increase acidity in the blood. As mammals produce carbon dioxide at a fast rate, it is vital that the body measures its levels so that breathing rates can be adjusted to exhale excess carbon dioxide and thus regulate blood pH within the narrow limits compatible with life.

Until now the body’s regulation of blood acid levels was thought to be triggered by measuring pH levels of the blood. However the new findings indicate that the body can sense carbon dioxide levels directly through Connexin 26.

“Carbon dioxide is the unavoidable by-product of our metabolic system—human beings and other mammals produce huge amounts of it every day,” says Dale.

“The exciting implication of our study is that carbon dioxide is much more than just a waste product: it can directly signal physiological information, and our work shows the mechanism by which this happens via Connexin 26.”

Connexin 26 comprises six identical subunits. Carbon dioxide makes a chemical bond to the side chain a particular amino acid. This modified side chain can then form a bridge to a closely oriented amino acid in the adjacent subunit. A total of six carbon dioxide molecules can bind to make six bridges between subunits. These bridges force the Connexin 26 protein to alter its conformation thereby signaling the presence and concentration of carbon dioxide.

The study appears in the journal eLife. Co-authors are Louise Meigh, Sophie Greenhalgh, and David Roper of the University of Warwick and Thomas Rodgers and Martin Cann of the University of Durham.

Source: Warwick University

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