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Howard  C.  Kutchai
Degree(s): Ph.D.
Graduate School: University of CA, San Franscisco
Primary Appointment: Professor of Molecular Physiology and Biological Physics
Research Interests:
Quaternary Structure of Na, K-ATPase and Its Regulatory Significance

Email Address: hck4p@virginia.edu
Biomedical Sciences Graduate Program(s)
  • Structural, Computational Biology and Biophysics
  • Molecular Medicine
  • Molecular Cell and Developmental Biology
    • Research Description

    The subject of our research is the calcium ATPase of sarcoplasmic reticulum of skeletal and cardiac muscle. We are investigating the hypothesis that the oligomeric state of the calcium ATPase in the sarcoplasmic reticulum membrane is of regulatory significance. The time dependence of the anisotropy of a covalent phosphorescent label on the calcium ATPase is used to estimate the mole fractions of monomeric, dimeric, tetrameric, and higher order oligomers of the calcium ATPase. Calcium, the inhibitors thapsigargin and cyclopiazonic acid, and local and general anesthetics have been found to modulate both the activity and the oligomeric state of the calcium ATPase. Thus far our results suggest that monomers and dimers of the calcium ATPase have full activity, but tetramers and larger aggregates have much less activity. More recently we have been studying the effects of local and general anesthetics on the activity and oligomeric state of the Na,K-ATPase of canine kidney. Local anesthetics strongly inhibit the activity of the Na,K-ATPase at anesthetic concentrations within the range at which they are used clinically. We will investigate whether inhibition of Na,K-ATPase contributes to the mechanism of action of local anesthetics.

    Selected Publications
  • Mueller, B.; Karim, C. B.; Negrashov, I. V.; Kutchai, H.; Thomas, D. D. Direct Detection of Phospholamban and Sarcoplasmic Reticulum Ca-ATPase Interaction in Membranes Using Fluorescence Resonance Energy Transfer. Biochemistry 43:8754-8765, 2004.
  • Mahaney, J.E., Albers, R.W., Kutchai, H., and Froehlich, J.P. Phospholamban controls Ca2+ pump oligomerization and intersubunit free energy exchange leading to activation of cardiac muscle SERCA2a. Annals of New York Academy of Sciences 986:338-340, 2003.
  • Kutchai, H. and Geddis. L.M. Inhibition of the activity of the Na,K-ATPase of canine renal medulla by several local anesthetics. Pharmacological Research 43:399-403, 2001.
  • Kutchai, H., Geddis, L.M., and Farley, R.A. Effects of local anesthetics on the activity of the Na,K-ATPase of canine renal medulla. Pharmacological Research 41:1-7, 2000.
  • PubMed Listings for this Faculty Member
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    Contact Information
      Office Address: PO Box 800736, Health Sciences, 4-38 Jordan Hal, 
      Office Phone: +1 434-924-2195
      Fax Phone: +1 434-982-1616

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