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Cell Physiology and Molecular Biophysics

Photograph of Dr. Artigas  
 

Pablo Artigas, Ph.D.

Associate Professor of Cell Physiology & Molecular Biophysics
Member of Center for Membrane Protein Research

Department of Cell Physiology
Texas Tech University Health Sciences Center
3601 4th Street, STOP 6551
Lubbock, Texas 79430
Phone: (806) 743-1142
Lab: (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 two main subjects. 1) Understanding how the Na/K and H/K pump works 2) elucidating the relationship between the lipid bilayer’s physical properties and the function and pharmacology of ion transporting proteins

Techniques

We use an array of techniques that include electrophysiology (patch-clamp
two-electrode voltage clampand 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, NSF, Center for Membrane Protein Research (TTUHSC), Laura W. Bush Institute for Women’s Health.
Past: South Plains Foundation, American Heart Association.

   Lab
Lab Members Collaborators (funded collaborations)
Technician
Michaela Jansen, Pharm.D., Ph.D., Associate Professor
Department of Cell Physiology & Molecular Biophysics and CMPR, TTUHSC
Victoria Young 
Graduate Students
Ina Urbatsch, Ph.D., Associate Professor
Department of Cell Biology & Biochemistry and CMPR, TTUHSC
Dylan Meyer
Undergraduate Students
Craig Gatto, Ph.D., Professor
Director, School of Biological Sciences, Illinois State University
Kerri Spontarelli
Med. Students
Sharan Bijlani
Grace Shim
Bente Vilsen, Ph.D., Professor 
Department of Biomedicine, Aahrus University, Denmark

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
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