The designed research is a multidisciplinary analysis of the modulation of the potassium currents in granule and mitral cells of the olfactory bulb. The broad, long-term objective of this research is to elucidate how neurotropins, growth factors, and cytoplasmic protein kinases can utilize ion channels as substrates for phosphorylation to give rise to short-term and long-term plastic changes in synaptic efficacy or to aid in the establishment of neural circuits in the olfactory bulb neurons, Kvl.3, using electrophysiological, biochemical, and molecular approaches. We will electrophysiologically examine changes in current magnitude and gating kinetics induced by activating tyrosine phosphorylation in granule and mitral cells and measure the degree of tyrosine specific phosphorylation. By utilizing the cloned Kvl.3 as a model, combined biochemical measurement of kinase-induced tyrosine phosphorylation and molecular mutagenesis will elucidate the mechanistic details of multiple phosphorylation of the ion channel. The proposal will provide new important information regarding the molecular mechanism for the convergence of multiple phosphorylation on an ion channel prominently expressed in the olfactory bulb, a brain region for which neuromodulation by phosphorylation is completely undescribed.
