Elucidating the roles played by the auditory and vestibular efferent systems is an important objective of current inner ear neuroscience. The proposed research will contribute to a better understanding of efferent effects on sensory hair cells at the molecular level through analysis of amino acid sequence and functional domains of the alpha9 acetylcholine receptor. The principal objectives of the proposed training period is to obtain a complete DNA sequence of the alpha9 nicotinic acetylcholine receptor from trout saccular hair cells, and to begin functional domain analysis through comparisons with what is known from other species about alpha9 and other alpha-type nicotinic acetylcholine receptors. To make appropriate extrapolations to human health and disease, contemporary research has made use of a wide variety of animal model systems. The trout sacculus provides an advantageous model where a hair cell sheet containing thousands of hair cells can be readily dissected and studied. This model system lends itself particularly well to biochemical and molecular biological questions that require adequate numbers of a single cell type. Functional domain analysis of the alpha9 receptor protein can only be enhanced by knowing the molecular structure of alpha9 receptor proteins from diverse species. Detailed comparisons of alpha9 protein structure across widely separated species should provide a rich source of clues into the molecular bases of alpha9 receptor function.
| Drescher, D G; Ramakrishnan, N A; Drescher, M J et al. (2004) Cloning and characterization of alpha9 subunits of the nicotinic acetylcholine receptor expressed by saccular hair cells of the rainbow trout (Oncorhynchus mykiss). Neuroscience 127:737-52 |
