Modulation of spike generation in somatosensory endings of the cornea - the role of chloride currents in inflammatory sensitization

• Antragsteller: Professor Dr. Stephan Frings
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2012 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 213632774

Afferent signals arising from sensory end organs are subject to considerable modulation even before reaching the spinal cord. Sensory neurons may adapt, they may be sensitized, or may even be overtly switched on or off. The molecular processes underlying such regulation have attracted considerable research effort but have only rarely been deciphered in detail. In the somatosensory system of mammals, the response characteristics of individual primary sensory neurons can be altered dramatically by the immune system. Inflammatory mediators sensitize nerve terminals and boost the intensity of stimulus-induced afferent signals. Based on recent concepts of peripheral inflammatory hyperalgesia, we examine the hypothesis that such sensitization is promoted by depolarizing chloride currents.To explore the effects of chloride currents in primary afferent neurones, we will analyse somatosensory fibres in the cornea of the mammalian eye. In two parallel and complementary approaches, we will study the expression of chloride transporters and chloride channels in corneal axons and, at the same time, examine chloride-related aspects of spike generation in corneal nerve terminals. The two approaches are designed to clarify two questions: (1) Which protein equipment mediates chloride effects in somatosensory nerve terminals; and (2) how are these proteins involved in the sensitization of nerve terminals during inflammation? To address these questions we combine studies of protein expression and protein regulation with the determination of nerve terminal sensitivity in the presence of inflammatory mediators. This project will add considerably to our understanding of plasticity in the somatosensory system through a novel approach to peripheral hyperalgesia.

• DFG-Verfahren: Sachbeihilfen
• Beteiligte Person: Privatdozent Dr. Richard Carr