Project: Research project

Project Details


Gap junctions are found between cells of most tissues, where they provide
intercellular channels that are permeable to a wide range of small
hydrophilic molecules. In the heart and nervous system, gap junctions allow
rapid and faithful transmission of electrical current that is carried by
junction permeant ions. The function of gap junctions in other tissues is
not as clear, and analysis of physiological roles is complicated by the
recent discovery that gap junction proteins are encoded by a family of
genes and that various gap junction channels have different properties.
Project I seeks to correlate properties of gap junctions with the
junctional proteins and to extend our understanding of the role of gap
junction channels in several tissues where previous work has been
incomplete. For selected tissues (endothelial cells, smooth muscle from
myometrium and vascular beds, skin (keratinocytes), pancreatic islet,
melanocytes and retinal pigment epithelium, and lens fibers) effects of
hormones and other agents on junctional conductance will be chosen for
their relevance to normal and altered physiological functions.
Nevertheless, the goals of these studies are similar: to determine the
identity of tissue-specific connexins using biochemical and immunological
techniques to identify the proteins and in situ hybridization and Northern
blot analysis to identify the mRNAs. For each tissue, electrophysiological
techniques will be used to identify single channel and macroscopic
conductances of channels that correspond to the connexins.
Electrophysiological studies will analyze mechanisms of regulation of
junctional conductance in each system, and together with studies of second
messenger effects on protein phosphorylation should indicate the potential
flexibility in intercellular signaling through these channels as a
consequence of this covalent modification. Physiological and
pharmacological studies will determine classes of agents that affect
intercellular communication and will compare response of cells containing
identified connexins. By examining whether junctional conductance is
regulated under conditions of physiological stimulation and pathological
insult, we hope to gain further insight into the roles that gap junctions
play in normal and diseased tissue.
Effective start/end date1/1/016/30/02


  • Genetics
  • Physiology
  • Medicine(all)
  • Neuroscience(all)
  • Animal Science and Zoology
  • Neurology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Molecular Biology
  • Structural Biology
  • Electrical and Electronic Engineering
  • Biochemistry
  • Behavioral Neuroscience
  • Cell Biology
  • Histology
  • Pharmacology
  • Immunology


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