There are two principal areas of research in the Hemmings laboratory: mechanisms of general anesthetic drugs and cell signaling. General anesthetics have important presynaptic effects on the release of neurotransmitters that affect synaptic transmission. We have demonstrated neurotransmitter- and anesthetic agent-specific effects on neurotransmitter release that involve effects on presynaptic ion channels. The specific ion channels affected and the mechanisms of these effects are currently under investigation.
The pharmacology and toxicology of general anesthetics are remarkably incomplete for such a widely used and clinically important class of drugs. Despite their widespread clinical use, our understanding of the molecular and cellular mechanisms of general anesthetic action in the central nervous system is insufficient to explain how any anesthetic produces amnesia, unconsciousness, or immobilization (with increasing doses), the cardinal clinical features of general anesthesia.
Anesthetics have potent and specific effects on synaptic transmission, including both presynaptic actions on the release of neurotransmitters and postsynaptic actions on their receptors. Our research aims to understand the presynaptic mechanisms of anesthetic effects on neurotransmitter release. Understanding synaptic mechanisms of anesthetics is essential for development of anesthetics with improved side-effect profiles and for optimization of current anesthetic techniques in high-risk patients. Current focus is on the region- and transmitter-specific actions and Na+ channel blocking mechanisms of volatile anesthetics. Such studies are essential to a molecular understanding of presynaptic anesthetic mechanisms and the balance between desirable and potentially toxic anesthetic effects on excitatory and inhibitory synaptic transmission.
Research areas:
Mechanisms of general anesthesia, neuropharmacology, synaptic transmission, sodium channel pharmacology, protein phosphorylation, regulation of protein phosphatases, cerebral ischemia and neuroprotection