PHYSIOLOGY OF RECONSTITUTED GAP JUNCTION CHANNELS

Project Details

Description

The gap junction is the locus of direct transfer of ions and small
molecules from cell to cell. It is composed of an array of protein
molecules in the plasma membranes of two abutting cells which form an
aqueous channel connecting the cytoplasms of the cells. On the basis of
intriguing circumstantial evidence, it is widely held that the
intercellular communication mediated by junctional channels must be
important in the normal development and mature function of many tissues.
Recently it has become clear that the conductance and permeability of the
junctional channel can be dynamically regulated by voltage, pH, calcium
ions and cyclic nucleotides. Therefore information about how the channel
functions, how it is gated, and what goes through it is likely to be of
interest beyond its biophysical aspects. The proposal is directed toward the study of junctional channels from rat
liver reconstituted in planar lipid bilayers. It builds on (1) past work
which characterized the gating properties of junctional channels in
cellular membranes using electrophysiological methods, and (2) preliminary
experiments in which channels with many of the properties of junctional
channels were incorporated into planar bilayers, with isolated gap
junctions as the starting material. It is proposed to (a) improve the
efficiency of the reconstitution, (b) to study the gating and selectivity
of the reconstituted junctional channels, specifically regarding voltage,
pH and osmotic effects (c) to test antisera against junctional protein for
functional effects on reconstituted channels, ad (d) to incorporate into
lipid bilayers the products of in vitro translation of RNA coding for
junctional protein. Through such studies of channel physiology, one hopes to understand the
mechanisms by which cells can modulate this form of intercellular
communication. Coupling by way of gap junctions is so widespread that
elucidation of this process will undoubtedly have profound effects in many
areas of cellular and developmental biology.
StatusFinished
Effective start/end date1/1/866/30/10

Funding

  • National Institutes of Health: $272,782.00
  • National Institutes of Health: $288,507.00
  • National Institutes of Health
  • National Institutes of Health: $125,681.00
  • National Institutes of Health: $295,450.00
  • National Institutes of Health: $259,190.00
  • National Institutes of Health: $283,640.00
  • National Institutes of Health
  • National Institutes of Health: $264,835.00
  • National Institutes of Health: $280,140.00
  • National Institutes of Health
  • National Institutes of Health: $143,609.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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