Paul A. Davies, PhD
Assistant Professor, Harvard Medical School
Presently, I am engaged in work that uses the patch-clamp technique to investigate new ligand-gated ion channels that have been discovered in the human genome. I was part of the team to first describe and characterize new subunits belonging to the serotonin (5-HT3B subunit) and GABA-gated (epsilon subunit) classes of ion channels in addition to discovering a brand new ion channel, ZAC.
In collaboration with Dr. Douglas Raines, we have been investigating the modulation of human homomeric 5-HT3A and heteromeric 5-HT3AB receptors by halogenated volatile anesthetics and alcohols. Post-operative nausea and vomiting is associated with the use of volatile anesthetics and can be treated with 5-HT3 receptor antagonists. Studying the interactions of anesthetics with these receptors may allow new anesthetic agents to be designed without the present side effects.
Craving for ethanol in early-onset alcoholics can be reduced by treatment with 5-HT3 receptor antagonists. Ethanol interacts with 5-HT3 receptors, but the molecular mechanisms of this interaction are unknown. I am currently investigating the molecular interactions of ethanol with 5-HT3 receptors by using single-channel recording techniques where we can record individual ion channels and examine how their activity is changed in the presence of ethanol.
Recently, I have been characterizing a new class of ligand-gated ion channel (ZAC) that is activated by zinc or copper and is expressed in discreet brain regions and peripheral tissues, including stomach, lung and trachea. ZAC is expressed in the CA3 and dentate gyrus of the hippocampus, areas associated with synaptically stored zinc and copper. Excess zinc and copper in these regions are also linked to neurotoxicity in Alzheimer's Disease, ischemia and epilepsy. We are currently examining the pharmacology of ZAC, including its modulation by alcohols and anesthetics.
Doug Raines, MD Profile
Pharmacology of Anesthesia
Department of Anesthesia, Critical Care and Pain Medicine
55 Fruit Street
Boston, MA 02114