Richard Hite
Emory University, BS
Harvard University, PhD
Lipid regulation of voltage-dependent K+ (Kv) channels
Voltage-dependent K+ (Kv) channels are the primary regulators of cellular membrane potential in electrically excitable cells. In response to electrical stimulation, Kv channels open and close, allowing cells rapidly to restore resting potential. Voltage-dependant K+ channels are integral membrane proteins, fully embedded in the hydrophobic lipid bilayer. Recent studies have shown that in addition to providing a hydrophobic solvent for Kv channels, lipids can also modulate channel gating. In fact, new data suggest that a given Kv channel can exhibit distinct behaviors in different cell types as a result of differences in membrane lipid composition. Also, variations in the lipid composition of the membrane in a single cell type over time due to metabolic influences may bring about changes in the function of Kv channels. Thus, lipid regulation of Kv channel function may turn out to be a new and fundamentally important pathway through which cell electrical excitability is controlled. The molecular details of the lipid-channel interactions, however, are currently unknown. In order to study the interactions between lipids and Kv channels I am using a combination of electrophysiology and structural biology. Electrophysiology has been used to screen and identify lipid species that specifically modulate channel gating and activity, while structural methods will be used to identify molecular interactions between lipids and the channel. These experiments are performed using Paddle Chimera, a well-characterized eukaryotic Kv channel comprised of rat Kv1.2 with the paddle domain of rat Kv2.1. In addition to providing insights into the modulation of membrane proteins by lipids, these results will also help to reveal the structural relationships between membrane potential and channel gating.
