Recently, Nature Medicine published the latest research findings of Activation of BK channels may not be required for bitter tastant-induced bronchodilation by researchers from the Institute of Model Animal Research, Nanjing University, Wenzhou Medical School, and University of Massachusetts Medical School (click for full article). In the article, the researchers further propose a different viewpoint in response to an important previous result on the mechanism of bitter tastant-induced bronchodilation in the lung, suggesting that BK channel activation may not be required for bitter tastant-induced bronchodilation. The authors of the article are Min-Sheng Zhu from Nanjing University and Rong-Hua Zhuge from the University of Massachusetts Medical School. The former graduated from the Fourth Military Medical University and is interested in studying the mechanism of smooth muscle contraction at the systems biology level: smooth muscle is a major component of the hollow organism and its contractile function is the basis of the physiological function of the organ in which it is located. If the contraction function is abnormal, it can cause a series of diseases, such as gastrointestinal diseases, cardiovascular abnormalities, bronchial asthma, etc. It is generally believed that mammals have five basic taste sensations, namely: sour, sweet, bitter, salty and fresh (umami). Studies have shown that people can perceive sour, sweet, bitter, salty and fresh tastes because of the presence of these five taste receptors (taste receptor (TR)) in taste buds. So far, researchers have identified only fresh taste and bitter taste receptors. In 2010, researchers from the University of Maryland School of Medicine reported that bitter taste receptors exist not only in the mouth but also in the human lungs, and they found that the taste receptors in the lungs are structurally identical to those in the tongue, although they differ greatly in function. Taste receptors on the tongue are often clustered in taste buds and transmit taste signals directly to the brain. Taste receptors in the lungs, however, do not accumulate in clusters and do not transmit signals directly to the brain, but rather respond to substances with a bitter taste. The researchers suggest that bitter taste increases intracellular calcium concentrations – to levels similar to those produced by the bronchoconstrictor drugs: histone and bradykinin (BK) – but triggers significant bronchodilation, suggesting that the increased calcium concentration inhibits contraction, contrary to the classical calcium-dependent mechanism previously described In contrast, this study found that the bitter compound elevated the calcium concentration but negatively relaxed the bronchial muscles in a unique way, contrary to the previous classical calcium-dependent mechanism, which assumes that increased calcium in smooth muscle causes muscle contraction. To explain this, the researchers propose that bitterness produces local calcium events and that bitterness-induced muscle relaxation, as well as polarization, can be inhibited by large-conductance Ca2+-activated K+, a BK channel antagonist called iberiotoxin. They therefore suggested that bitterness-induced bronchodilation is due to its local calcium signal, and that this signal turns on BK channels, allowing cell membrane polarization. But this idea involving BK channel activation is based only on the role of iberiotoxin in bitter-induced muscle relaxation and the cell membrane potential indicated by voltage-sensitive dyes. In the latest study, the researchers concluded that the association between BK channel activity and muscle relaxation was not directly demonstrated, raising questions about the mechanism of muscle relaxation. The researchers therefore further analyzed the role of bitterness in BK channel activation and, in mouse airway smooth muscle, the muscle relaxation effects of multiple BK channels, ultimately finding that BK channel activation may not be a necessary element for bitterness-induced bronchodilation. The researchers propose that some bitter compounds can act with human and mouse airway smooth muscle cells, and all of them can open the airways with effects even stronger than those of drugs used to treat asthma or chronic obstructive pulmonary disorders. Therefore, they could be used to develop new drugs for asthma, emphysema or chronic bronchitis. These new drugs would have the potential to replace or promote the drugs being used, which is a completely different and new approach to treatment.