Abstract

We plan to continue our investigation of the changes in electrophysiological behavior that give rise to abnormal rhythms of the heart and that accompany the termination of abnormal rhythms. Intracellular microelectrodes are used to record membrane potentials and to inject current in small Purkinje fibers, and in small strips of coronary sinus tissue, both isolated from dog hearts. Both types of preparation are studied in a fast perfusion system to allow rapid alteration of the ionic composition of the extracellular solution or rapid addition or removal of drugs. We plan to use our detailed knowledge of the characteristics of electrogenic sodium extrusion in Purkinje fibers to identify the contribution made by pump current to the Purkinje fiber action potential and to analyze the actions of drugs which possibly alter pump activity. We plan also to continue our study of steady-state currents flowing through excitable channels in the membrane of Purkinje cells. We plan to continue our studies of the factors determining the excitability of cells in the coronary sinus, including the effects of epinephrine on the resting potential and on the appearance of after-depolarizations and triggering.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL014899-15
Application #
3334856
Study Section
Cardiovascular Study Section (CVA)
Project Start
1977-09-01
Project End
1988-03-31
Budget Start
1986-09-01
Budget End
1988-03-31
Support Year
15
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Hwang, T C; Nagel, G; Nairn, A C et al. (1994) Regulation of the gating of cystic fibrosis transmembrane conductance regulator C1 channels by phosphorylation and ATP hydrolysis. Proc Natl Acad Sci U S A 91:4698-702
Gadsby, D C; Hwang, T C; Baukrowitz, T et al. (1994) Regulation of CFTR channel gating. Jpn J Physiol 44 Suppl 2:S183-92
Gadsby, D C; Hwang, T C; Horie, M et al. (1993) Cardiac chloride channels: incremental regulation by phosphorylation/dephosphorylation. Ann N Y Acad Sci 707:259-74
Hwang, T C; Horie, M; Gadsby, D C (1993) Functionally distinct phospho-forms underlie incremental activation of protein kinase-regulated Cl- conductance in mammalian heart. J Gen Physiol 101:629-50
Gadsby, D C; Nakao, M; Bahinski, A et al. (1992) Charge movements via the cardiac Na,K-ATPase. Acta Physiol Scand Suppl 607:111-23
Horie, M; Hwang, T C; Gadsby, D C (1992) Pipette GTP is essential for receptor-mediated regulation of Cl- current in dialysed myocytes from guinea-pig ventricle. J Physiol 455:235-46
Hwang, T C; Horie, M; Nairn, A C et al. (1992) Role of GTP-binding proteins in the regulation of mammalian cardiac chloride conductance. J Gen Physiol 99:465-89
Gadsby, D C; Noda, M; Shepherd, R N et al. (1991) Influence of external monovalent cations on Na-Ca exchange current-voltage relationships in cardiac myocytes. Ann N Y Acad Sci 639:140-6
Gadsby, D C; Nakao, M; Bahinski, A (1991) Voltage-induced Na/K pump charge movements in dialyzed heart cells. Soc Gen Physiol Ser 46:355-71
Cranefield, P F; Aronson, R S (1991) Torsades de pointes and early afterdepolarizations. Cardiovasc Drugs Ther 5:531-7

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