Effekte volatiler Anästhetika auf spannungsgesteuerte Natriumkanäle

• Applicant: Dr. Karl Herold
• Subject Area: Anaesthesiology
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 36063896

General anesthetics are widely used clinically, yet their molecular mechanisms have not been completely revealed. Gaining more information on their cellular and molecular effects will facilitate development of more specific anesthetics with fewer side-effects, thus increasing patient safety. It has been shown that volatile anesthetics reduce the release of neurotransmitters via effects on presynaptic ion-channels. Considerable evidence supports the view that blockade of presynaptic voltage-gated sodium (Na+) channels contributes to anesthetic inhibition of transmitter release in cerebral cortex. The overall aim of our research is to elucidate the mechanisms by which volatile anesthetics affect neurotransmitter release. The specific aims of this project are (A) to characterize the electrophysiological effects of the volatile anesthetic isoflurane on specific subtypes of wild-type Na+ channels, (B) to determine the effects of site-specific mutations of voltage-gated Na+ channels on sensitivity to volatile anesthetics and (C) to determine the role of phosphorylation in anesthetic effects on Na+ channels using patch-clamp electrophysiological methods in order to clarify the mechanisms of anesthetic blockade.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Hugh Hemmings