Abstract

This is a program to study the Cell Biology of Striated Muscle. It was established in 1977 to support a program combining biochemical, physiological and ultrastructural approaches to the understanding of control of excitation and contraction in cardiac and skeletal muscle. Five project leaders develop general inter-related themes, including: - functional role and developmental pattern of myosin heavy chain isozymes, especially their response to circulatory and hormonal influences. - characterization of the genes coding for myosin heavy chains and for membrane channels, and determination of the factors controlling the gene expression. - kinetic properties of the actomyosin interaction, its regulation, and its relationship to cross-bridge events during contraction. - structural basis of conduction, including the cardiac gap junction and the sarcolemmal transport and Na-channel proteins, and their functional counter parts in cardiac cells under voltage clamp. - control of intracellular calcium and its relation to tension in muscle. These studies are organized into six projects and three core facilities. We have had significant progress in defining the structure-function relationships and the genetic control of several important components of the surface membrane and the contractile system.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL020592-17
Application #
3097765
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1977-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
17
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Hilber, Karlheinz; Sandtner, Walter; Zarrabi, Touran et al. (2005) Selectivity filter residues contribute unequally to pore stabilization in voltage-gated sodium channels. Biochemistry 44:13874-82
Sandtner, Walter; Szendroedi, Julia; Zarrabi, Touran et al. (2004) Lidocaine: a foot in the door of the inner vestibule prevents ultra-slow inactivation of a voltage-gated sodium channel. Mol Pharmacol 66:648-57
Undrovinas, Albertas I; Maltsev, Victor A; Kyle, John W et al. (2002) Gating of the late Na+ channel in normal and failing human myocardium. J Mol Cell Cardiol 34:1477-89
Hilber, Karlheinz; Sandtner, Walter; Kudlacek, Oliver et al. (2002) Interaction between fast and ultra-slow inactivation in the voltage-gated sodium channel. Does the inactivation gate stabilize the channel structure? J Biol Chem 277:37105-15
Hilber, K; Sandtner, W; Kudlacek, O et al. (2001) The selectivity filter of the voltage-gated sodium channel is involved in channel activation. J Biol Chem 276:27831-9
Penzotti, J L; Lipkind, G; Fozzard, H A et al. (2001) Specific neosaxitoxin interactions with the Na+ channel outer vestibule determined by mutant cycle analysis. Biophys J 80:698-706
Sunami, A; Glaaser, I W; Fozzard, H A (2001) Structural and gating changes of the sodium channel induced by mutation of a residue in the upper third of IVS6, creating an external access path for local anesthetics. Mol Pharmacol 59:684-91
Martin, R L; Lee, J H; Cribbs, L L et al. (2000) Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther 295:302-8
Sunami, A; Glaaser, I W; Fozzard, H A (2000) A critical residue for isoform difference in tetrodotoxin affinity is a molecular determinant of the external access path for local anesthetics in the cardiac sodium channel. Proc Natl Acad Sci U S A 97:2326-31
Dudley Jr, S C; Chang, N; Hall, J et al. (2000) mu-conotoxin GIIIA interactions with the voltage-gated Na(+) channel predict a clockwise arrangement of the domains. J Gen Physiol 116:679-90

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