Weak Acids Irritate Ion Channel

Another group of chemicals—weak acids—has just been added to the list of stimuli that elicit a response from TRPA1, an ion channel in cell membranes that is involved in sensing environmental irritants, according to a report in the Journal of General Physiology (DOI: 10.1085/jgp.201110615). Found in the sensory neurons of the oral and nasal cavities, TRPA1 typically detects reactive electrophiles such as cinnamaldehyde and acrolein when they bind to the protein receptor’s terminal cysteine groups. Emily R. Liman of the University of Southern California and coworkers, however, demonstrate that TRPA1 senses weak acids on the basis of changes in the pH of cells’ inner fluid, or cytosol. The researchers found that weak acids such as acetic and propionic acid cross the cell membrane in an undissociated form and activate the ion channel from the inside with protons that they release. The TRPA1 residues involved in the mechanism are, so far, unknown. The “sheer diversity” of TRPA1 activators, writes Brandeis University neurobiologist Paul A. Garrity in an accompanying commentary on the report, “makes understanding the mechanisms by which this channel is regulated a fascinating and important goal.”