Abstract

This application will investigate whether: 1) The K+ channel underlying the resting membrane potential of DA smooth muscle changes during development from a calcium-dependent K+ channel to a voltage-gated delayed rectifier channel; 2) Increased oxygen inhibits the voltage regulated K+ channels, but not calcium-regulated K+ channels, to initiate vasoconstriction; and 3) The change in the K+ channel setting the resting membrane potential determines the stage in fetal development at which the DA constricts to oxygen. Potassium channels will be studied in fetal rabbit DA cells using both whole-cell and single channel patch-clamp techniques. Functional studies will be carried out on isolated DA vascular rings.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29HL059182-01
Application #
2441288
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1998-02-01
Project End
2002-01-31
Budget Start
1998-02-01
Budget End
1999-01-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Physiology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Porter, V A; Rhodes, M T; Reeve, H L et al. (2001) Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of K(Ca) channels. Am J Physiol Lung Cell Mol Physiol 281:L1379-85
Reeve, H L; Tolarova, S; Nelson, D P et al. (2001) Redox control of oxygen sensing in the rabbit ductus arteriosus. J Physiol 533:253-61
Peterson, D A; Reeve, H L; Nelson, D et al. (2001) Triple-bonded unsaturated fatty acids are redox active compounds. Lipids 36:431-3
Reeve, H L; Michelakis, E; Nelson, D P et al. (2001) Alterations in a redox oxygen sensing mechanism in chronic hypoxia. J Appl Physiol 90:2249-56
Cornfield, D N; Saqueton, C B; Porter, V A et al. (2000) Voltage-gated K(+)-channel activity in ovine pulmonary vasculature is developmentally regulated. Am J Physiol Lung Cell Mol Physiol 278:L1297-304
Porter, V A; Reeve, H L; Cornfield, D N (2000) Fetal rabbit pulmonary artery smooth muscle cell response to ryanodine is developmentally regulated. Am J Physiol Lung Cell Mol Physiol 279:L751-7
Reeve, H L; Nelson, D P; Archer, S L et al. (1999) Effects of fluoxetine, phentermine, and venlafaxine on pulmonary arterial pressure and electrophysiology. Am J Physiol 276:L213-9
Reeve, H L; Archer, S L; Soper, M et al. (1999) Dexfenfluramine increases pulmonary artery smooth muscle intracellular Ca2+, independent of membrane potential. Am J Physiol 277:L662-6