Research Abstract:
Research in this laboratory is focused on delineating the molecular mechanisms controlling the expression, properties and functioning of voltage-gated K+ (Kv) channels in cardiac and neuronal cells. These channels determine the heights and the durations of action potentials, shape repetitive firing properties and mediate the responses to synaptic inputs. In addition, these channels are important targets for regulation and modulation by transmitters and hormones. Investigators in this lab exploit a sophisticated combination of biochemical, electrophysiological, immunohistochemical and molecular techniques to define the properties of the Kv channels expressed in different cells and to identify the molecular correlates of these channels. Exploiting in vitro and in vivo approaches, recent studies have identified the role of individual Kv pore-forming a subunits in the generation of functional Kv channels and defined the roles of individual Kv channels in neuronal and myocardial cell functioning. Ongoing studies are focused on defining the functional roles of accessory Kv b subunits, exploring Kv channel trafficking and the molecular mechanisms underlying physiological and pathophysiological Kv channel remodeling.
Selected Publications:
Marionneau C, Brunet S, Flagg TP, Pilgram TK, Demolombe S.and Nerbonne JM. Distinct cellular and molecular mechanisms underlie functional remodeling of repolarizing K+ currents with left ventricular hypertrophy. Circ Res 2008 102: 1406-1415.
Niwa N, Wang W, Sha Q, and Nerbonne JM. Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles. J Mol Cell Cardiol 2008 44: 95-104.
Nerbonne JM, Gerber BR, Mellor RL, and Burkhalter A. Electrical remodeling maintains firing properties in cortical pyramidal neurons lacking KCND2-encoded A-type K+ currents. J Physiol 2008 586: 1565-1579.
Marionneau C, Aimond F, Brunet S, Niwa N, Finck B, Kelly DP, and Nerbonne JM. PPARa-mediated remodeling of repolarizing voltage-gated K+ (Kv) channels in a mouse model of diabetic cardiomyopathy. J Mol Cell Cardiol 2008 44: 1002-1015.
Laezza F, Gerber BR, Lou J.-L, Kozel M, Hartman H, Craig AM, Ornitz DO, and Nerbonne JM. The FGF14 (F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability. J Neurosci 2007 27: 12033-12044.
Last Updated: 07/28/2008 |