Abstract

Gap junctions consist of ensembles of intercellular channels that mediate electrotonic, metabolic, and dye coupling among cells of many tissues. Conductance through gap junction channels of fish and amphibian embryos is gated by transjunctional voltage, cytoplasmic pH, and to a lesser extent, by Ca ions. By the combined use of electrophysiological and optical techniques we intend to determine whether these gating mechanisms are common to other cell types, localize gating regions of the channel macromolecule, correlate junctional conductance with permeability and determine biophysical properties of individual gap junction channels. Although no disease state is now attributable to alterations in gap junctions, role in pathological conditions have been postulated (e.g., cataract formation, tumorigenesis, cardiac arrhythmias). Detailed analysis of permeation of gap junction channels may indicate the plausibility of a role in pathology and also provide information generalizable to other smaller ion channels.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS023241-01
Application #
3406501
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Arts and Sciences
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Zhou, Xiaoming; Yin, Wu; Doi, Sonia Q et al. (2003) Stimulation of Na,K-ATPase by low potassium requires reactive oxygen species. Am J Physiol Cell Physiol 285:C319-26
Okamura, H; Yasuhara, J C; Fambrough, D M et al. (2003) P-type ATPases in Caenorhabditis and Drosophila: implications for evolution of the P-type ATPase subunit families with special reference to the Na,K-ATPase and H,K-ATPase subgroup. J Membr Biol 191:13-24
Wilson, P D; Devuyst, O; Li, X et al. (2000) Apical plasma membrane mispolarization of NaK-ATPase in polycystic kidney disease epithelia is associated with aberrant expression of the beta2 isoform. Am J Pathol 156:253-68
Kostich, M; Fire, A; Fambrough, D M (2000) Identification and molecular-genetic characterization of a LAMP/CD68-like protein from Caenorhabditis elegans. J Cell Sci 113 ( Pt 14):2595-606
Zhou, X; Fambrough, D M (1999) Expression of the avian Na,K-ATPase subunits in Dictyostelium discoideum. J Membr Biol 167:19-24
Gough, N R; Zweifel, M E; Martinez-Augustin, O et al. (1999) Utilization of the indirect lysosome targeting pathway by lysosome-associated membrane proteins (LAMPs) is influenced largely by the C-terminal residue of their GYXXphi targeting signals. J Cell Sci 112 ( Pt 23):4257-69
Colonna, T E; Huynh, L; Fambrough, D M (1997) Subunit interactions in the Na,K-ATPase explored with the yeast two-hybrid system. J Biol Chem 272:12366-72
Ishii, T; Hata, F; Lemas, M V et al. (1997) Carboxy-terminal regions of the sarcoplasmic/endoplasmic reticulum Ca(2+)- and the Na+/K(+)-ATPases control their K+ sensitivity. Biochemistry 36:442-51
Feng, Y; Huynh, L; Takeyasu, K et al. (1997) The Drosophila Na,K-ATPase alpha-subunit gene: gene structure, promoter function and analysis of a cold-sensitive recessive-lethal mutation. Genes Funct 1:99-117
Gough, N R; Fambrough, D M (1997) Different steady state subcellular distributions of the three splice variants of lysosome-associated membrane protein LAMP-2 are determined largely by the COOH-terminal amino acid residue. J Cell Biol 137:1161-9

Showing the most recent 10 out of 33 publications