Effects of volatile anesthetic on channel structure of gramicidin A.
Volatile anesthetic agent, 1-chloro-1,2,2-trifluorocyclobutane (F3), was found to alter gramicidin A channel function by enhancing Na(+) transport (. Biophys. J. 77:739-746). Whether this functional change is associated with structural alternation is evaluated by circular dichroism and nuclear magnetic resonance spectroscopy. The circular dichroism and nuclear magnetic resonance results indicate that at low millimolar concentrations, 1-chloro-1,2,2-trifluorocyclobutane causes minimal changes in gramicidin A channel structure in sodium dodecyl sulfate micelles. All hydrogen bonds between channel backbones are well maintained in the presence of 1-chloro-1,2,2-trifluorocyclobutane, and the channel structure is stable. The finding supports the notion that low affinity drugs such as volatile anesthetics and alcohols can cause significant changes in protein function without necessarily producing associated changes in protein structure. To understand the molecular mechanism of general anesthesia, it is important to recognize that in addition to structural changes, other protein properties, including dynamic characteristics of channel motions, may also be of functional significance.
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 USA. tangp@anes.upmc.edu
Pei
P
Tang
Pravat K
PK
Mandal
Martha
M
Zegarra
D000777:Anesthetics / Q000494:pharmacology; D017402:Chlorofluorocarbons / Q000494:pharmacology; D002942:Circular Dichroism; D003503:Cyclobutanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006096:Gramicidin / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D007473:Ion Channels; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D011522:Protons; D012964:Sodium / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014364:Tryptophan / Q000737:chemistry
D000777:Anesthetics; D017402:Chlorofluorocarbons; D003503:Cyclobutanes; D007473:Ion Channels; D008823:Micelles; D011522:Protons; D006096:Gramicidin; D012967:Sodium Dodecyl Sulfate; C107485:1-chloro-1,2,2-trifluorocyclobutane; D014364:Tryptophan; D012964:Sodium