The main goal of this project lies in identifying agonists for two transient receptor potential (TRP) ion channels that are potentially involved in inner ear mechanosensation. One of the major obstacles of inner ear biology is the lack of specific pharmacological tools to investigate the process of mechanotransduction of inner ear sensory hair cells. Although the vertebrate hair cell transduction channel remains a mystery, a number of TRPs are connected to a potential physiological function in the inner ear. Particularly TRPML3 and TRPN1, the focus of this application, have been shown to be important for hearing and balance in mice and zebrafish. Identification of agonists and, in future studies prospective antagonists, would not only advance inner ear and sensory neurobiology, but could also provide us with potential drug candidates for the treatment of vertigo and tinnitus. ? ? ?
| Grimm, Christian; Jörs, Simone; Guo, Zhaohua et al. (2012) Constitutive activity of TRPML2 and TRPML3 channels versus activation by low extracellular sodium and small molecules. J Biol Chem 287:22701-8 |
| Grimm, Christian; Jors, Simone; Saldanha, S Adrian et al. (2010) Small molecule activators of TRPML3. Chem Biol 17:135-48 |
