This award supports a three year collaborative research project between Professor James Trimmer of the State University of New York (SUNY) at Stony Brook and Professor Kazuhiro Ikenaka of the Okazaki National Research Institutes in Japan. The researchers will be undertaking a study of the mechanisms of ion channel targeting in the mammalian nervous system. Proper levels of expression and localization of ion channels is required for the propagation of signals in the nervous system. In mammalian central neurons, voltage-gated K+ channels play a crucial role in regulating the resting membrane potential, impacting dendritic excitability, controlling the frequency and duration of action potentials, and modulating neurotransmitter release. Neurons synthesize a great variety of K+ channels that are fundamental components of neuronal activity patterns. This research is aimed at determining the molecular mechanisms that regulate the abundance and distribution of voltage-dependent K+ channels. The proposed studies focus on determining the auxiliary subunits that regulate the expression of the Kv4 channels that comprise the dendritic "A" current, and the axonal proteins that localize Kv1 channels to the juxtaparanodal regions of nodes of Ranvier.
This project brings together the efforts of two laboratories that have complementary expertise and research capabilities. The U.S. researchers' expertise is in the area of biochemistry and immunohistochemistry and the Japanese have expertise in the area of genetics. Results of this research would provide a for a better understanding of protein channel subunit expression and interaction in neuronal systems, and its potential biomedical implications in mammalian and human neuronal disease. This research advances international human resources through the participation of a younger scientist and graduate students. Through the exchange of ideas and technology, this project will broaden our base of basic knowledge and promote international understanding and cooperation. ***