Ion channels gated by heat

All animals need to sense temperature to avoid hostile environments and to regulate their internal homeostasis. A particularly obvious example is that animals need to avoid damagingly hot stimuli. The mechanisms by which temperature is sensed have until recently been mysterious, but in the last couple of years, we have begun to understand how noxious thermal stimuli are detected by sensory neurons. Heat has been found to open a nonselective cation channel in primary sensory neurons, probably by a direct action. In a separate study, an ion channel gated by capsaicin, the active ingredient of chili peppers, was cloned from sensory neurons. This channel (vanilloid receptor subtype 1, VR1) is gated by heat in a manner similar to the native heat-activated channel, and our current best guess is that this channel is the molecular substrate for the detection of painful heat. Both the heat channel and VR1 are modulated in interesting ways. The response of the heat channel is potentiated by phosphorylation by protein kinase C, whereas VR1 is potentiated by externally applied protons. Protein kinase C is known to be activated by a variety of inflammatory mediators, including bradykinin, whereas extracellular acidification is characteristically produced by anoxia and inflammation. Both modulatory pathways are likely, therefore, to have important physiological correlates in terms of the enhanced pain (hyperalgesia) produced by tissue damage and inflammation. Future work should focus on establishing, in molecular terms, how a single ion channel can detect heat and how the detection threshold can be modulated by hyperalgesic stimuli.

Health impacts of domestic coal use in China

Domestic coal combustion has had profound adverse effects on the health of millions of people worldwide. In China alone several hundred million people commonly burn raw coal in unvented stoves that permeate their homes with high levels of toxic metals and organic compounds. At least 3,000 people in Guizhou Province in southwest China are suffering from severe arsenic poisoning. The primary source of the arsenic appears to be consumption of chili peppers dried over fires fueled with high-arsenic coal. Coal samples in the region were found to contain up to 35,000 ppm arsenic. Chili peppers dried over high-arsenic coal fires adsorb 500 ppm arsenic on average. More than 10 million people in Guizhou Province and surrounding areas suffer from dental and skeletal fluorosis. The excess fluorine is caused by eating corn dried over burning briquettes made from high-fluorine coals and high-fluorine clay binders. Polycyclic aromatic hydrocarbons formed during coal combustion are believed to cause or contribute to the high incidence of esophageal and lung cancers in parts of China. Domestic coal combustion also has caused selenium poisoning and possibly mercury poisoning. Better knowledge of coal quality parameters may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals and macerals in coal may help predict the behavior of the potentially toxic components during coal combustion.