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Alex M. Dopico, MD, PhD

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


  • PhD Institution: University of Buenos Aires, Argentina, Pharmacology
  • MD Institution: University of Buenos Aires, Argentina, Medicine

Research Interests

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. 

Representative Publications

  • Bukiya AN, Dopico AM. Cannabinoid Interactions with Proteins: Insights from Structural Studies. Adv Exp Med Biol. 2019;1162:39-50. doi: 10.1007/978-3-030-21737-2_3. Review. PubMed PMID: 31332733.
  • Simakova M, Tobiasz A, Sullivan RD, Bisen S, Duncan J, Sullivan JP, Davison S, Tate DL, Barnett S, Mari G, Dopico AM, Bukiya AN. Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries. J Drug Alcohol Res. 2019;8. pii: 236068. doi: 10.4303/jdar/236068. PubMed PMID: 31057979; PubMed Central PMCID: PMC6497414.
  • Bukiya AN, Dopico AM. Regulation of BK Channel Activity by Cholesterol and Its Derivatives. Adv Exp Med Biol. 2019;1115:53-75. doi: 10.1007/978-3-030-04278-3_3. Review. PubMed PMID: 30649755.
  • North KC, Chang J, Bukiya AN, Dopico AM. Extra-endothelial TRPV1 channels participate in alcohol and caffeine actions on cerebral artery diameter. Alcohol. 2018 Dec;73:45-55. doi: 10.1016/j.alcohol.2018.04.002. Epub 2018 Apr 26. PubMed PMID: 30268908; PubMed Central PMCID: PMC6417832.
  • Bisen S, Simakova MN, Dopico AM, Bukiya AN. Large conductance voltage- and calcium-gated potassium channels (BK) in cerebral artery myocytes of perinatal fetal primates share several major characteristics with the adult phenotype. PLoS One. 2018 Sep 13;13(9):e0203199. doi: 10.1371/journal.pone.0203199. eCollection 2018. PubMed PMID: 30212531; PubMed Central PMCID: PMC6136719.
  • North K, Bisen S, Dopico AM, Bukiya AN. Tyrosine 450 in the Voltage- and Calcium-Gated Potassium Channel of Large Conductance Channel Pore-Forming (slo1) Subunit Mediates Cholesterol Protection against Alcohol-Induced Constriction of Cerebral Arteries. J Pharmacol Exp Ther. 2018 Nov;367(2):234-244. doi: 10.1124/jpet.118.250514. Epub 2018 Aug 16. PubMed PMID: 30115756; PubMed Central PMCID: PMC6170972.

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May 26, 2022