Cell Physiology and Molecular Biophysics
Pablo Artigas, Ph.D.
Associate Professor of Cell Physiology & Molecular Biophysics
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
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.
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.
||Collaborators (funded collaborations)
Department of Cell Physiology & Molecular Biophysics and CMPR, TTUHSC
Department of Cell Biology & Biochemistry and CMPR, TTUHSC
Dominique Gagnon, Ph.D., Instructor
Department of Physics, TTU
|| Dana Phillips, M.D., F.A.C.O.G, Associate Professor, Department of Obstetrics and Gynecology
Department of Biochemistry & Molecular Biophysics University of Chicago
|Attilio Di Nunnon
| Jaanki Khandelwal
Director, School of Biological Sciences, Illinois State University
| Kerri Spontarelli
Job openings. If interested, please send letter of intent, CV and contact for reference letters
to Pablo Artigas.
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.
- Stanley CM, Gagnon DG, Bernal A, Meyer DJ, Rosenthal JJ, Artigas P. Importance of
Voltage Dependence of Cardiac Na/K ATPase Isozymes (2015). Biophys J. 109:1852-62.
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.