University of Arkansas, Fayetteville


Channels in cell membranes are important for intercellular communication and especially for the function of the nervous system in higher vertebrates. These channels consist of proteins made from the 20 common amino acids. Channel proteins are embedded into the lipid bilayer membranes of living cells and function by allowing the specific passage of a positively charged material such as sodium or potassium ions across the membrane in response to an external signal. The external signaloeither a chemical signal or a voltageoregulates the opening and closing of channels. In an attempt to understand the voltage-dependent opening of channels (igatingi), we are investigating model membrane-spanning channels whose properties can be regulated by voltage. Our laboratory has developed the only chemically defined model system for which it is currently possible to investigate the structural basis for the voltage gating response at the molecular level. Our iwindowi into the gating process involves deuterium magnetic resonance spectroscopy. We use a small model channel system that we label with deuterium (iheavy hydrogeni) by specific chemical synthesis and then align in liquid-crystalline arrays of hydrated lipid bilayer membranes. The most novel aspect of this research is the ambitious goal of recording magnetic resonance spectra in the presence of a voltage across a stack of oriented, liquid-crystalline membranes. Experiments toward this goal will be described in our article. Accomplishments to date have prepared the way for the voltage-dependent magnetic resonance experiments. To this end, a series of gated and non-gated (control) channel-forming peptides have been designed, synthesized and incorporated into oriented, hydrated lipid/peptides samples. Spectra that define open and closed channel states have been recorded in the absence of a voltage. An important penultimate step has been the successful replacement of the water of hydration by glycerol in preparation for the voltage-dependent spectroscopy.