The proposal outlines plans to continue study of electrophysiologic properties and underlying mechanisms of ion transport in embryonic cultured chick heart cells. Besides the direct contributions of electrodiffusive and electrogenic transport, the indirect contribution of electroneutral transport to the electrophysiological properties will also be considered. Results of several experimental techniques will be integrated to establish a functional relationship between active transport by the Na-K pump and the overall regulation of ion gradient-coupled transport mechanisms, e.g., Na-Ca, Na-H exchange. Techniques include: H-ouabain binding; Na-K ATPase sensitive monoclonal antibody; K tracer kinetics; voltage-clamp; K, Na selective microelectrodes; electron microscopy with energy dispersive x-ray spectrophotometric and fluorometric determinations of Nai, Ki, Cai, Cat, Hi; electro-optical monitoring of contractions will also be carried out. Adaptive changes in the capacity of the Na-K pump will be used to study physiologic implications of active Na-K transport on cardiac cell function. The Na-K pump will be characterized in terms of its rate constant, maximum capacity, ouabain-binding properties, stoichiometry and its dependence on K and membrane potential. The long term goal is to enhance our understanding of the magnitude and interplay of ion exchange fluxes and active transport processes in regulating electrochemical and electrophysiologic properties of cardiac muscle. Adaptive changes in Na-K transport should provide new information relating in vivo reaction processes to hypokalemia as well as to therapeutic and toxic levels of cardiac glycosides.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL027105-06
Application #
3338949
Study Section
Cardiovascular Study Section (CVA)
Project Start
1981-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Souza, M M; Gross, S; Boyle, R T et al. (2000) Na+/K+-ATPase inhibition during cardiac myocyte swelling: involvement of intracellular pH and Ca2+. Mol Cell Biochem 210:173-83
Souza, M M; Boyle, R T; Lieberman, M (2000) Comparisons of different stages of chick embryonic development by the physiological regulatory response to hyposmotic challenge. Comp Biochem Physiol A Mol Integr Physiol 125:451-8
Souza, M M; Boyle, R T; Lieberman, M (2000) Different physiological mechanisms control isovolumetric regulation and regulatory volume decrease in chick embryo cardiomyocytes. Cell Biol Int 24:713-21
Boyle, R T; Lieberman, M (1999) Permeabilization by streptolysin-o reveals a role for calcium-dependent protein kinase c isoforms alpha and beta in the response of cultured cardiomyocytes to hyposmotic challenge. Cell Biol Int 23:685-93
Zhang, J; Larsen, T H; Lieberman, M (1997) F-actin modulates swelling-activated chloride current in cultured chick cardiac myocytes. Am J Physiol 273:C1215-24
Hall, S K; Zhang, J; Lieberman, M (1997) An early transient current is associated with hyposmotic swelling and volume regulation in embryonic chick cardiac myocytes. Exp Physiol 82:43-54
Zhang, J; Lieberman, M (1996) Chloride conductance is activated by membrane distention of cultured chick heart cells. Cardiovasc Res 32:168-79
Hall, S K; Zhang, J; Lieberman, M (1995) Cyclic AMP prevents activation of a swelling-induced chloride-sensitive conductance in chick heart cells. J Physiol 488 ( Pt 2):359-69
Liu, S; Stimers, J R; Lieberman, M (1994) A novel Cl- conductance in cultured chick cardiac myocytes: role of intracellular Ca2+ and cAMP. J Membr Biol 141:59-68
Wagenknecht, B; Freudenrich, C C; LeFurgey, A et al. (1994) Calcium depletion and repletion in cultured chick heart muscle cells. J Mol Cell Cardiol 26:797-808

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