MOLECULAR PHYSIOLOGY OF ION CHANNELS

The research in the laboratory is focused on the molecular mechanisms governing the function of membrane-spanning ion permeable channels. These questions are addressed using a combination of electrophysiological studies on ion channel function (and structure) and spectroscopic studies of channel structure, in conjunction with theoretical/computational studies on channel folding, ion permeation, and channel-bilayer interactions. The main tool in the laboratory is the family of gramicidin channels, which offer a unique combination of advantages that sets them apart from all other ion channels: the channel structure is known at atomic resolution, which guides the experimental design; one can obtain structural information about sequence-modified channels using functional (single-channel) measurements; single-channel measurements provide direct information about the channels' catalytic ability; and gramicidin channels can be used as molecular force transducers to quantify the energetics of channel-membrane interactions. The aim is to understand how the primary amino acid sequence and the anisotropic lipid bilayer environment interact in determining the structure and function of membrane-spanning channels. For example, how are the rates of ion movement and the ion selectivity determined by the channel's amino acid sequence and structure; specifically, what are the structural and functional consequences of the interfacial localization of the aromatic amino acids? Another aim is to understand how a structural "stress," introduced by sequence modifications, affects channel dynamics; specifically, how modest sequence alterations introduce voltage control of channel function. Other experiments probe how alterations in the host bilayer alter channel function; specifically how alterations in a bilayer's material properties alter the distribution between different channel conformations. The knowledge thus acquired is used to explore how alterations in membrane lipid composition, such as those that occur during a coronary occlusion, affect the gating of gramicidin channels as well as voltage-dependent ion channels formed by integral membrane proteins. Can the alterations in channel gating be related to alterations in the host bilayer's material properties?e-mail: sparre@med.cornell.eduFor more information, please visit:http://physiology.med.cornell.edu/faculty/andersen/index.html

Dr. Andersen is a faculty member in the Tri-Institutional PhD Program in Chemical Biology.