CARDIAC GAP JUNCTIONS--CONTROL OF EXPRESSION &FUNCTION

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date7/1/906/30/91

Funding

  • National Heart, Lung, and Blood Institute

ASJC

  • Cardiology and Cardiovascular Medicine
  • Physiology

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