TTUHSC School of Medicine
HomeSchool of MedicinePharmacology and NeuroscienceFaculty

Pharmacology and Neuroscience

Dr. Michael P. Blanton

Professor and Vice-Chair of Pharmacology
Ph.D., 1989, University of California, Santa Cruz

Curriculum Vitae

Structure/Function of Ligand-Gated Ion Channels and P-type Ion-Motive ATPases:

LGIC: The nicotinic acetylcholine, serotonin (5-HT3), γ-aminobutyric acid type A (GABAA), and glycine receptors belong to a superfamily of ligand-gated ion channels (LGIC) each being critical for rapid signal transduction in the nervous system. In addition, each of these receptors constitute important target sites for many therapeutic drugs. Research in the lab is focused on two overall objectives: First, to determine how each of these ligand-gated ion channels function. More specifically, to identify and characterize the different structural elements, including the lipid-protein interface, that mediate each aspect of receptor function. To determine how each of these elements interact to effect the overall functioning of the receptor. Inclusive in this first goal is work aimed at determining in detail the structure of AChR functional elements (e.g. ion channel, lipid-protein interface. Secondly, to determine how drugs, in particular both local and general anesthetics (and neurosteroids), interact with each of the LGIC family members. Inclusive in this goal is not only understanding what are the determinants of drug binding but what are the mechanisms by which the binding of these ligands effect the structure of the receptor both locally as well as distally (i.e. allosterically). To accomplish these goals a wide array of techniques are employed in the laboratory and with collaborators, including: photoaffinity labeling, protein chemistry, spectroscopy (CD, FTIR, Fluorescence), as well as molecular biological and electrophysiological techniques.

Hks3s Cal28ks

Figure 1: Molecular Model of the barbiturate Pentobarbital complexed with the Nicotinic Acetylcholine Receptor Ion Channel. (from Arias et al., (2001) Molecular Pharmacology 60, 497-506)

Na,K-ATPases: The Na,K-ATPase is present in the plasma membrane of nearly all animal cells where it couples the hydrolysis of ATP to the transport of Na+ ions out of cells and K+ ions into cells, thereby establishing an electrochemical gradient. The ion gradients created by the Na,K-ATPase are fundamental to many diverse cellular functions, including fluid and electrolyte balance in animals. Research in the lab is focused on two major goals: 1) Identify membrane-spanning segments and individual amino acid residues which contribute to the formation of the lipid-protein interface of the ATPase. The research design is to covalently tag lipid-exposed residues of the Na,K-ATPase using the hydrophobic photoreactive compound 3-trifluoromethyl-3-(m-[125I]iodophenyl) diazirine ([125I]TID) as well as with photoreactive lipid analogs of cholesterol and phosphatidylserine. Lipid-exposed segments and amino acids are to be determined by N-terminal sequencing of isolated proteolytic fragments. Furthermore, preliminary results with [125I]TID have established that the extent of labeling of the Na,K-ATPase is conformationally-sensitive. There is increased [125I]TID incorporation into the Na,K-ATPase in the E2 conformation and the enhanced labeling maps to proteolytic fragments which contain the M5 and M6 transmembrane segments. 2) The second goal is to then identify [125I]TID labeled residues in the M5 and M6 segments in both the E1 and E2 conformations of each ATPase, residues which are putatively located in the cation occlusion domain of each ATPase and are therefore part of the cation translocation pathway.

Hks3s Cal28ks

Figure 2: Mapping the sites of [125I]TID photoincorporation into the Na,K-ATPase (from Blanton and McCardy (2000) Biochemistry 39, 13534-13544).

For a complete list of publications by Michael P. Blanton in PubMed, click here

For further information contact Dr. Michael P. Blanton

Download Free Adobe Reader Get Adobe Reader Adobe Acrobat Reader is required to view items marked with this icon:
Please click on the left image to download the free version.