JCI online early table of contents: April 8, 2008

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Phone: (443) 690-4129; Fax: (410) 614-8216; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34333

PULMONARY

Understanding how nerves sense chemicals that irritate the lungs

A subset of nerves that terminate in the lining of the airways constantly monitor the air that we breathe for chemicals that might threaten airway function. These sensory nerves are particularly sensitive to the oxidants that form in polluted air and to chlorine, which is often released in industrial accidents, and their stimulation by exposure to such chemicals causes coughing, sneezing, stuffiness, and pain. Although this response is normally protective, it can be dangerous in patients with compromised lung function, such as those suffering from asthma.

In a new study, Sven-Eric Jordt and colleagues from the Yale University School of Medicine, New Haven, have shown that mice lacking the TRPA1 protein, which is involved in signaling inflammatory pain, have decreased depression of the breathing rate and decreased pain following exposure to chlorine and oxidant chemicals. These results indicate that TRPA1 may mediate the response of airway sensory nerves to upper airway irritants. The authors therefore suggest that drugs that inhibit TRPA1 function may help patients with exaggerated responses to chemical irritants, such as those with asthma.

TITLE: TRPA1 is a major oxidant sensor in murine airway sensory neurons

AUTHOR CONTACT:

Sven-Eric Jordt

Yale University School of Medicine, New Haven, Connecticut, USA.

Phone: (203) 785-2159; Fax: (203) 737-2027; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34192

MUSCLE BIOLOGY

Establishing how a genetic mutation can cause disease

Congenital myasthenias are inherited disorders characterized by muscle weakness caused by mutations in genes that contain the information for making proteins that are involved in the communication between nerves and muscle cells. For example, some individuals with congential myasthenia have mutations in the genes that contain the information for making the subunits of a protein that is expressed by muscle cells and that binds a molecule known as acetylcholine, which is the transmitter by which nerves convey signals to the muscle. In a new study, Andrew Engel and colleagues, at the Mayo Clinic, Rochester, determined how a mutation in the gene containing the information for making the delta-subunit of the receptor for acetylcholine, which they detected in a patient with congenital myasthenia, might lead to the disease. The mutation was found to cause a change in the structure of the acetylcholine receptor, leading to slower opening of the receptor, which in turn slowed ion flow through the channel and thus impaired muscular function.

TITLE: Congenital myasthenia–related AChR-delta subunit mutation interferes with intersubunit communication essential for channel gating

AUTHOR CONTACT:

Andrew G. Engel

Mayo Clinic, Rochester, Minnesota, USA.

Phone: (507) 284-5102; Fax: (507)284-5831; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34527