 Biological membranes are thin, flexible barriers made of protein and
lipid that both envelop cells and divide them into compartments. Communication
across these barriers is achieved by transport proteins, including ion
channels. Faculty and students in the Department of Biomedical Sciences
are engaged in studies of several intracellular channels in order to understand
basic mechanisms like selectivity and gating, that is, how the channels
open and close in response to stimuli like membrane voltage and drugs.
Carmen Mannella and Kathleen Kinnally investigate the membranes of mitochondria, the cell's power plants. Dr. Mannella applies electron crystallography and other techniques to the gated channel called VDAC, or porin, through which metabolites and drugs enter the organelle. He also uses electron tomography to study the internal organization of mitochondria and their interactions with other cell components. Dr. Kinnally applies techniques of electrophysiology to mitochondrial channels, in particular, patch-clamping, which involves direct measurements of minuscule ion currents that flow through the channels. One such channel, called MCC, is involved in protein uptake by the organelle and, in response to certain signals, may activate abnormally and trigger events in the complex pathway of programmed cell death.Terence Wagenknechtstudies a calcium channel in the sarcoplasmic reticulum called the ryanodine receptor, which plays a major role in excitation-contraction (e-c) coupling, the process by which muscles are stimulated to contract by nerve impulses. Using high-resolution electron microscopy and image processing, he is determining the intricate structure of this calcium release channel in different states, and the complexes it forms with other proteins involved in e-c coupling.
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