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 NIH Neuroscience Series Seminar

Dr. Nerbonne’s research is focused ondelineating the molecular, cellular and systemic mechanisms involved in thedynamic regulation of cardiac and neuronal membrane excitability. Combiningbiochemical, electrophysiological, immunohistochemical and molecular genetic approaches,the focus of their work is on characterizing the biophysical properties and thefunctional roles of the voltage-gated potassium (Kv) and sodium (Nav) ionchannels expressed in different myocardial and neuronal cell types, definingthe functional roles of these channels in shaping the waveforms of individualaction potentials and controlling repetitive and rhythmic firing, identifyingthe molecular correlates of native neuronal and myocardial Kv and Nav channels,and delineating the mechanisms controlling channel expression, distribution and functioning.

Using a variety of molecular geneticstrategies and proteomics, ongoing studies are focused on defining the roles ofKv channel accessory subunits and regulatory proteins in controlling thefunctional cell surface expression and the biophysical properties of Kvchannels in the normal heart. Similar approaches are exploited to define themolecular determinants of myocardial Nav channel expression and functioning.Additional ongoing studies are focused on exploring the molecular mechanismsunderlying Kv and Nav channel remodeling in the hypertrophied and failing heartand in other myocardial diseases associated with cardiac rhythm disturbances.

The other major goal of ongoing research in their laboratoryis to define the mechanisms that control the expression and functioning ofnative neuronal Kv and Nav channels. These channels function to controlneuronal resting membrane potentials, action potential waveforms, repetitivefiring, the responses to synaptic inputs and synaptic plasticity. In ongoingstudies, they are exploring the molecular basis of functional neuronal Kv andNav channel diversity and the mechanisms controlling the expression,trafficking, localization and biophysical properties of these channels inneurons in the cerebellum, suprachiasmatic nucleus and cerebral cortex.