Hugh C Hemmings

The long-term goal of the proposed research is to identify the mechanisms of the effects of inhaled anesthetics on synaptic transmission as an approach to improving the pharmacological specificity of these notoriously promiscuous drugs. My laboratory has taken a systematic approach to identifying anesthetic effects on neurotransmission by first characterizing their presynaptic effects on transmitter release, followed by targeted studies of the mechanisms underlying these effects. The current proposal builds on our prior studies by focusing in depth on the role of ion channels, and of voltage-gated Na+ channels in particular, in the effects of anesthetics on presynaptic Ca2+ entry and exocytosis in mammalian neurons, and now extends these studies to intracellular Ca2+ regulation and neuronal subtype-specific effects. I have a broad background in neuroscience, neuropharmacology and anesthesiology with experience in the key research areas of this proposal as a PI that qualifies me to carry out the proposed studies. I have successfully administered this project for the last 20 years making fundamental discoveries important to the cellular and molecular effects of general anesthetics on synaptic transmission. The current proposal builds on this prior work incorporating new approaches and collaborations to understand the synaptic mechanisms of inhaled anesthetics from the cellular to the molecular level.