Alex M. Dopico, M. D., Ph.D.
Distinguished Professor and Chair
Department of Pharmacology
The University of Tennessee Health Science Center
874 Union Avenue
Memphis, TN 38163
Fax: (508) 448-7206
Lab: 207 Crowe Research Building
Email: Alex M. Dopico
- Ph.D. Institution: University of Buenos Aires, Argentina, Pharmacology
- M.D. Institution: University of Buenos Aires, Argentina, Medicine
My laboratory is interested in determining the mechanism of action of small amphiphilic compounds on ion channels from excitable cells. One of these amphiphiles is alcohol, the most widely used and abused drug. Some others are physiological modulators, such as bile acids and neurosteroids. Our current research is focused on two projects dealing with large conductance, Ca++-activated K+ (BK) channels. These channel proteins have been demonstrated to be involved in both controlling central neuron excitability and regulating arterial smooth muscle tone. Project 1: To determine the molecular basis for differential actions of alcohol on BK channels from mammalian brain vs. arterial smooth muscle, including modulation of drug action by membrane lipids. Project 2: To determine the structural requirements (both in the amphiphile molecule and the ion channel protein) for the modulation of arterial muscle BK channels by bile acids.
For these studies we combine electrophysiological and molecular biology techniques. Ion channel responses to drug exposure are evaluated in: 1) freshly isolated cells, where we study drug modification of channel behavior in the native environment of the channel protein; 2) isolated patches of cell membrane, where we can address the differential role of different membrane-bound vs. cytosolic second messengers in drug action; 3) artificial bilayers of controlled lipid composition, where we can determine the modulatory role of membrane lipids in drug action.
Ion channel isoforms from relevant tissue are identified. Following mRNA isolation and cloning, channel subunits of known sequence are expressed in heterologous systems such as Xenopus oocytes or HEK-293 cells. Then, we can determine the role of channel subunit composition in drug action by studying drug effects on ion channel complexes that differ in pore-forming and/or modulatory subunit composition. In addition, differential responses to a drug by channels that differ in a given region of a subunit, when studied in the same proteolipid environment, allow us to postulate sites in that subunit for drug recognition. This is probed by studying drug action on expressed channel proteins that include mutations in the postulated region(s).
My laboratory is interested in determining the molecular mechanism of action of alcohol and other small amphiphiles on ion channel proteins from the brain and arterial vessels. To determine the recognition sites for alcohol in these proteins and how alcohol modifies protein function upon interaction with these sites, will provide critical information for understanding how the drug interacts with its targets and, eventually, lead to the design of clinically useful agents to treat conditions associated with alcohol intake.
- Wei W, Ding S, Zhou FM. Dopaminergic treatment weakens medium spiny neuron collateral inhibition in the parkinsonian striatum. J Neurophysiol. 2016 Dec 7:jn.00683.2016. doi: 10.1152/jn.00683.2016. [Epub ahead of print] PubMed PMID: 27927785.
- Tian B, Wang XL, Huang Y, Chen LH, Cheng RX, Zhou FM, Guo R, Li JC, Liu T. Peripheral and spinal 5-HT receptors participate in cholestatic itch and antinociception induced by bile duct ligation in rats. Sci Rep. 2016 Nov 8;6:36286. doi: 10.1038/srep36286. PubMed PMID: 27824106; PubMed Central PMCID: PMC5099756.
- Zhou FM, Cheng RX, Wang S, Huang Y, Gao YJ, Zhou Y, Liu TT, Wang XL, Chen LH, Liu T. Antioxidants Attenuate Acute and Chronic Itch: Peripheral and Central Mechanisms of Oxidative Stress in Pruritus. Neurosci Bull. 2016 Oct 25. [Epub ahead of print] PubMed PMID: 27783328.
- Cao LF, Peng XY, Huang Y, Wang B, Zhou FM, Cheng RX, Chen LH, Luo WF, Liu T. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease. Neural Plast. 2016;2016:6383240. PubMed PMID: 27747105; PubMed Central PMCID: PMC5056271.
- Broussard JI, Yang K, Levine AT, Tsetsenis T, Jenson D, Cao F, Garcia I, Arenkiel BR, Zhou FM, De Biasi M, Dani JA. Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus. Cell Rep. 2016 Mar 1;14(8):1930-9. doi: 10.1016/j.celrep.2016.01.070. PubMed PMID: 26904943; PubMed Central PMCID: PMC4772154.
- Li L, Sagot B, Zhou FM. Similar L-dopa-stimulated motor activity in mice with adult-onset 6-hydroxydopamine-induced symmetric dopamine denervation and in transcription factor Pitx3 null mice with perinatal-onset symmetric dopamine denervation. Brain Res. 2015 Jul 30;1615:12-21. doi: 10.1016/j.brainres.2015.04.011. PubMed PMID: 25960345.