Graduate Training in Neuroscience
University of Washington
Bruce L. Tempel
Associate Professor, Departments of Otolaryngology-HNS and Pharmacology (joint)
Research in the Tempel lab uses molecular, genetic and electrophysiological techniques to study the functional roles of voltage-gated potassium (Kv) channels in the nervous system, focusing on signal encoding in the auditory system. Molecular techniques are used to study Kv channel gene expression and regulation as well as the localization of specific Kv channels in auditory neurons. In addition, the lab has generated mice carrying targeted deletions of specific Kv channel genes. Among these "knock out" mice, the Kv1.1-null mutation causes epilepsy as well as hearing loss, providing a unique model for studying the role of a specific Kv channel gene in controling neuronal hyperactivity as well as in preserving action potential synchrony in auditory neurons.
A second approach to understanding the molecular basis of hearing uses positional cloning techniques to identify genes causing deafness in mice. Of particular interest to us is the deafwaddler mutant which affects the physiological function of hair cells. Recently, we identified mutations in a calcium ATPase gene in deafwaddler and are now studying the role of this gene in auditory and vestibular function.
Finally, we are interested in the molecular mechanisms of Kv channel gene regulation. We have analyzed the gene structure and proximal promoter elements for Kv1.1, IRK1 and Kv1.2, identifying unique tissue specific promoter and repressor elements. In addition, we have discovered that Kv channels are regulated at the translational level. For example, receptor-stimulated increases in cAMP cause the rapid degradation of Kv1.1 mRNA in glia; changes that may affect cell proliferation and differentiation.
Mutations in plasma membrane Ca2+-ATPase PMCA2 cause deafness in deafwaddler mice. Left. ICC of PMCA2 (green) in presynaptic calyx of Held in Medial Nucleus of the Trapezoid Body (MNTB) a fast, secure synapse in the central auditory pathway that needs to clear calcium quickly to maintain signal fidelity. Right. ICC of PMCA2 (green) in cerebellar Purkinje neurons.