Research in Dr. Nerbonne’s laboratory explores the molecular, cellular and systemic mechanisms involved in the dynamic regulation of neuronal and cardiac membrane excitability. Investigators in the laboratory exploit a combination of biochemical, electrophysiological, immunohistochemical and molecular genetic techniques in studies focused on characterizing the voltage-gated ion channels expressed in different cell types, identifying the molecular correlates of these channels and delineating the molecular mechanisms controlling the expression, distribution and functioning of these channels.
A major focus of ongoing work is on defining the physiological roles of the various Ca++-independent, voltage-gated K+ (Kv) channels that control the heights and durations of action potentials in the myocardium and on determining the roles of these channels in the generation of normal cardiac rhythms. Using a variety of molecular genetic strategies and proteomics, ongoing studies are aimed at defining the roles of Kv channel accessory subunits and regulatory proteins in controlling the expression and the properties of Kv channels in the normal heart. Additional studies are focused on exploring the molecular mechanisms underlying Kv channel remodeling in the hypertrophied and failing heart and in other myocardial diseases associated with cardiac rhythm disturbances.
The other major focus of the research in the Nerbonne laboratory is on delineating the molecular mechanisms that control the expression, localization and functioning of Kv channels and voltage-gated Na+ (Nav) channels in neurons. Kv currents are key determinants of neuronal excitability, functioning to control resting membrane potentials, action potential waveforms, repetitive firing and the responses to synaptic inputs. Ongoing studies are focused on exploring the molecular basis of functional neuronal Kv and Nav channel diversity and on probing the molecular mechanisms controlling the properties, the expression, the trafficking and the distributions of these channels.