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Cell Physiology and Molecular Biophysics

Photograph of Dr. Artigas

Pablo Artigas, Ph.D.

Associate Professor of Cell Biology & Molecular Biophysics
Ph.D. in Biology, option Biophysics (2002).
University of the Republic, Montevideo, Uruguay

Department of Cell Physiology
Texas Tech University Health Sciences Center
3601 4th Street, STOP 6551
Lubbock, Texas 79430
Phone: (806) 743-3170
FAX: (806) 743-1512
Email: Pablo.Artigas@ttuhsc.edu


Research Interests

Our research focuses on understanding the function, mechanisms and pharmacology of the proteins that transport ions across membranes. They are essential for the electrical signaling in the cardiovascular and nervous systems, and as such, they represent the target of several pharmacological agents used for the treatment of a number of cardiovascular and neural diseases.


We study three main subjects. 1) Understanding how the Na/K pump works 2) elucidating the relationship between the lipid bilayer’s physical properties and the function and pharmacology of ion transporting proteins and 3) Uncovering the role ion transporting proteins in myometrium.

Techniques

We use an array of techniques that include electrophysiology (patch-clamp, two-electrode voltage clamp and cut-open oocyte), molecular biology (site-directed mutagenesis, heterologous protein expression and western blot), biochemistry (chemical modification, measurement of ATPase activity, radiolabeled ion uptake) and fluorescence microscopy (voltage clamp fluorometry, immunocytochemistry). 

Funding

We are thankful to all agencies (federal and private) that have supported our research.

Active: NIH, Center for Membrane Protein Research (TTUHSC), Laura W. Bush Institute for Women’s Health.
Past: NSF, South Plains Foundation, American Heart Association.

   Lab
Lab Members Collaborators (funded collaborations)
Technician
Michaela Jansen, Ph.D., Associate Professor
Department of Cell Physiology & Molecular Biophysics and CMPR, TTUHSC
Sukanyalakshmi Chebrolu
Graduate Students
Ina Urbatsch, Ph.D., Associate Professor
Department of Cell Biology & Biochemistry and CMPR, TTUHSC
Dylan Meyer
Chris Stanely
Dominique Gagnon, Ph.D., Instructor
Department of Physics, TTU
Kevin Stanley
Undergraduate Students  Naghma Farooqi, M.D., Assistant Professor
Department of Obstetrics & Gynecology, TTUHSC
Adam Bernal
Jessica Eastman
Benoit Roux, Ph.D., Professor
Department of Biochemistry & Molecular Biophysics University of Chicago
Jaanki Khandelwal
Jesse Astorga
Craig Gatto, Ph.D., Professor
Director, School of Biological Sciences, Illinois State University
Austin Lunney
Morgan Allen  

Job openings. If interested, please send letter of intent, CV and contact for reference letters to Pablo Artigas.

Na/K pump

Animal cells require maintaining concentration gradients for Na+ and K+ ions across the plasma membrane. These gradients, build solely by the Na/K pump, are essential for normal electrical transmission in excitable cells and for homeostasis in all cells. The Na/K pump is a heteromeric membrane protein, composed for an α and a β subunit, that catalyzes the extrusion of 3 Na+, in exchange for 2 K+, using the energy released by hydrolysis of one ATP molecule.
In humans Na/K pump isozymes may be formed by association of one of four α subunit with one of three β subunit isoforms, all with tissue specific distribution. In addition, also in a tissue specific manner, FXYD proteins can associate to the αβ complex to modulate the function of the Na/K pump. Malfunction due to spontaneous or inherited mutations of Na/K pump α isoforms is responsible for several illnesses including hypertension, hemiplegic migraine and dystonia parkinsonism. We are actively studying the reasons for isoform multiplicity and the mechanisms involved in illness induction by some of these mutations.
Moreover, the Na/K pump is the target of digitalis, a group of drugs widely used for more than 200 years for the treatment of congestive heart failure. It is thought that beneficial effects of digitalis involve selective inhibition of α2 pumps with slightly higher affinity than α1 pumps. Our studies will help to understand the mechanism of action of digitalis. Other projects in the lab aim at understanding how the pump selects its transported ions and the mechanism of actions of palytoxin.

Membrane-protein interaction and mechanisms of drug action

Many amphipathic compounds that are ingested by humans, either as medicines or with food affect the function of several membrane proteins (e.g. Na, K and Cl channels and Na/K pump) with similar concentration dependence.
Membrane proteins are set in a lipid bilayer matrix. To avoid exposure of hydrophobic groups to the polar aqueous environment, the span of the hydrophobic tails of the bilayer’s phospholipids must match the length of the hydrophobic residues of the embedded protein. Thus, when a protein conformation requires those two lengths to differ, the hydrophobic mismatch forces the bilayer to deform. Amphipathic compounds that insert within the bilayer may affect protein function by changing energetic cost associated with bilayer deformation instead of directly interacting with the proteins. Our research aims at identifying drugs that affect the bilayer, elucidating the changes in material properties induced by them and understanding the membrane-protein interaction responsible for these effects.
Currently, in collaboration with Inna Urbatsch, PhD, we are addressing how the bilayer physical properties affect the function of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the gene mutated in patients with cystic fibrosis.

Ion transporting proteins in myometrium

During labor, the uterus develops powerful and rhythmic contractions that are driven by changes in the voltage of the uterine muscle cells. Like in all excitable cells, membrane proteins, called ion channels, interplay to produce this electrical activity in uterine cells, but the molecular identity of these uterine channels is not fully understood. In collaboration with Dominique Gagnon, PhD and Maghma Farooqi, MD, we intend to fill this gap in knowledge by identifying the potassium channels involved in excitation-contraction coupling in the human uterus with an approach that combines cell culture, patch clamp electrophysiology, molecular biology and hystochemistry.


Selected Publications

  • Mitchell TJ, Zugarramurdi C, Olivera JF, Gatto C, Artigas P. (2014) Sodium and proton effects on inward proton transport through Na/K pumps. Biophys. J. 106:2555-65. Article selected as New and Notable. See associated         commentary by Hans Jurgen Apell.

  • Galva C, Artigas P, Gatto C. (2012) Nuclear Na+/K+-ATPase plays an active role in nucleoplasmic Ca2+ homeostasis. J Cell Sci 125:6137-47

  • Yu H, Ratheal IM, Artigas P, Roux B (2011) Protonation of key acidic residues is critical for the K(+)-selectivity of the Na/K pump. Nat Struct Mol Biol 18:1159-63

  • Ratheal I, Virgin G, Yu H, Roux B, Gatto C, Artigas P (2010). Selectivity of externally facing ion binding sites in the Na/K pump to alkali metals and organic cations. Proc Natl Acad Sci U S A. 107:18718-23

  • Yaragatupalli S, Olivera JF, Gatto C, and Artigas P (2009) Altered Na+ transport after an intracellular alpha-subunit deletion reveals strict external sequential release of Na+ from the Na/K pump. Proc Natl Acad Sci U S A. 106:15501-15512.

  • Gadsby DC, Takeuchi A, Artigas P, Reyes N. (2009). Review. Peering into an ATPase ion pump with single-channel recordings. Philos Trans R Soc Lond B Biol Sci. 364:229-38

  • Takeuchi A, Reyes N, Artigas P, Gadsby DC. (2008). The ion pathway through the opened Na(+),K(+)-ATPase pump. Nature 456:413-6

  • Rakowski RF, Artigas P, Palma F, Holmgren M, De Weer P, and Gadsby DC. (2007). Sodium flux ratio in Na/K pump-channels opened by palytoxin. J. Gen. Physiol. 130:41-54

  • Artigas P, Hobart EA, Díaz L, Al’Aref SJ, Straw S, Sakaguchi M, and Andersen OS. (2006). 2,3 butanedione monoxime affects CFTR channel function through phosphorylation-dependent and phosphorylation-independent Mechanisms. The role of bilayer material properties. Mol. Pharmacol. 70:2015-2026.

  • Artigas P and Gadsby DC. (2006). Ouabain affinity determining residues lie close to the Na/K pump ion pathway. Proc. Natl. Acad. Sci. 103:12613-12618.

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