GAP JUNCTIONS IN VASCULAR SMOOTH MUSCLE--GROWTH CONTROL

Project: Research project

Description

DESCRIPTION: Dr. Burt, a long contributor to the literature on gap junctional gating and regulation, proposes a detailed analysis of the response of gap junctional coupling to mitogenic stimuli (both acute and chronic) in three different cell lines. The basis of these investigations is an exciting finding by the PI that runs contrary to the general dogma that intercellular coupling is decreased during cellular proliferation. Instead, she has found that, comparing proliferating and growth arrested A7r5 cells, coupling as measured by dye spread decreases, but electrical coupling increases. This change is coincident with a change in the distribution of single channel conductances (increase in 150pS channel and decrease in 70pS channel) and inverse changes in the RNA levels of the two major connexins expressed in these cells (i.e. increase in Cx40 and decrease in 43). The hypothesis that arises from these data is that the proliferative state may need to retain electrical coupling, but depresses the exchange of larger metabolites and messengers, and achieves this through differential expression of connexins with varying permselectivities (it is assumed, without substantiation, that anionic preference would favor the relevant messenger system). Ultimately the proposal is directed towards defining a role for gap junctions in the proliferative responses associated with Atherosclerosis. Towards this end, the PI has partially characterized three cell systems--A7r5 cells, primary Smooth Muscle Cells (SMCs), and transfected HeLa cells--and established conditions for serum deprived growth arrest and PDGF and ox-LDL mitogenic stimulation.
StatusFinished
Effective start/end date7/15/9711/30/15

Funding

  • National Institutes of Health: $378,750.00
  • National Institutes of Health: $265,125.00
  • National Institutes of Health: $261,108.00
  • National Institutes of Health: $331,492.00
  • National Institutes of Health: $322,145.00
  • National Institutes of Health: $209,137.00
  • National Institutes of Health: $378,750.00
  • National Institutes of Health: $261,108.00
  • National Institutes of Health: $360,570.00
  • National Institutes of Health: $371,175.00
  • National Institutes of Health: $338,625.00
  • National Institutes of Health: $322,145.00
  • National Institutes of Health: $265,125.00
  • National Institutes of Health: $322,145.00
  • National Institutes of Health
  • National Institutes of Health: $194,768.00

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Gap Junctions
Vascular Smooth Muscle
Connexins
Connexin 43
Growth
Phosphorylation
Permeability
Wounds and Injuries
Cardiovascular System
Blood Vessels
Electrophysiology
Patch-Clamp Techniques
Peptides
Smooth Muscle Myocytes
Fluorescence Microscopy
Health
Peripheral Nervous System Diseases
Deafness
Tandem Mass Spectrometry
Cell Proliferation

ASJC

  • Medicine(all)