Gap junctions are low resistance channels that in cardiac tissue provide a pathway for impulse propagation and contraction synchrony. Considerable information is available on both short and long term regulation of gap junction in other tissues and has laid the groundwork for the application of similar techniques to cardiac tissue. We intend to combine several cell biological techniques including pharmacology, immunology and electrophysiology in order to study gating of gap junctions and expression of gap junction protein and function between cardiac cells. Pairs of isolated adult and neonatal ventricular myocytes will be used as experimental models. Antibodies are available with demonstrated reactivity against rat cardiac gap junction protein; a probe for cardiac gap junction mRNA is nearing availability. Using these probes, relative levels of junctional protein and mRNA will be determined by immunoblot and hybridization techniques and compared to dye coupling and junctional conductance (gj) under a variety of conditions expected to affect expression. We will also correlate phosphorylation of the immuno-identified junctional protein with changes in gj and its sensitivity to gating stimuli. Regulation of expression and activity of membrane proteins is a topic of general cell biological interest and in heart these studies may have considerable pathological relevance: It has long been suggested that conductance disturbances may involve abnormalities in gap junctions, which are the sites of lowest safety factor for impulse propagation among cardiac cells. These experiments should finally begin to answer the fundamental questions of how cardiac gap junctions are regulated and what role they play in propagation of electrical and metabolic activity in physiological and pathological states.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL038449-04
Application #
3354733
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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