Take a moment to think about how amazing it is that we can taste so many flavors in the meals we eat! Approximately ten thousand taste buds located on the surface of your tongue detect the five basic tastes: sweet, sour, salty, bitter, and umami. Each taste bud contains three different types of elongated taste cells (Type I, Type II, and Type III). Each of these sensory neurons has a different mechanism for transducing a specific taste signal to the brain. Type I glial-like cells detect the salty taste, while Type III presynaptic cells sense the sour taste. Type II receptor cells recognize sweet, bitter, and umami tastes by expressing different types of G protein-coupled receptors (GPCRs).
A distinct feature of Type II receptor cells is that they release ATP as a neurotransmitter to convey taste information to the brain. Since they lack conventional synaptic connections with nerves, the exact mechanism of ATP-mediated signal transduction was unknown. In an attempt to answer the question, researchers at the University of Pennsylvania extensively studied the molecular mechanism of Type II receptor cells and discovered a new ATP-releasing ion channel: calcium homeostasis modulator 1 (CALHM1).
Before this finding, it was believed that ATP release was mediated by gap junction hemichannels, which allow communication with neighboring cells, so that Type III presynaptic cells could generate taste responses. However, the team’s discovery of CALHM1 showed that this voltage-gated ion channel is specific to Type II receptor cells and is a crucial component for releasing ATP as a neurotransmitter for the perception of sweet, bitter, and umami tastes.
To do this, the research team generated mice that lacked CALHM1. It was hypothesized that these CALHM1-knockout mice would not be able to taste sweet, bitter, and umami. Generally, mice prefer to drink sucrose (sweet) water over plain water and tend to avoid bitter tastes. When CALHM1-knockout mice were tested for their taste preference, the researchers noted that the mice lost preference for sweet tastes and did not avoid bitter tastes! As a control, the research team also tested the taste preference of CALHM1-knockout mice toward salty and sour tastes, but those responses were unaffected. This further supported their hypothesis that CALHM1 mediates ATP release and is exclusively expressed in Type II receptor cells. In conjunction with the behavioral studies, the researchers also blocked the hemichannel and showed that ATP levels were unaffected, ruling out any possible contribution of the hemichannel.
This is an intriguing study because of the novel discovery of a channel that mediates ATP signaling in certain taste cells, a process that had not been fully understood until now. It is so exciting to see scientists approach a question from different points of view to discover what is really happening in a system!
Huang Y.J., Maruyama Y., Dvoryanchikov G., Pereira E., Chaudhari N. & Roper S.D. (2007). The role of pannexin 1 hemichannels in ATP release and cell-cell communication in mouse taste buds,Proceedings of the National Academy of Sciences, 104 (15) 6436-6441. DOI: 10.1073/pnas.0611280104.
Dando R. & Roper S.D. (2009). Cell-to-cell communication in intact taste buds through ATP signalling from pannexin 1 gap junction hemichannels, The Journal of Physiology, 587 (24) 5899-5906. DOI:10.1113/jphysiol.2009.180083.