Abstract

The major focus of this proposal is to determine if co-expression and subsequent formation of """"""""mixed"""""""" heterogeneous gap junction channels represents a unique pathway for the regulation of intercellular communication. The PI will study subunit connexin co-expression of Cx45, Cx43, and Cx40 in vitro. All are connexins found in specialized cardiac tissue and are thought to be critical to normal and abnormal cardiac rhythm, for example. Two experimental approaches will be used to assess the presence of heterogeneous channels. First dual whole cell patch clamp and extensive analysis of channel properties will be initiated. Second a connexin transgene expression system will be used to regulate the amount of each connexin produced. The PI will monitor/utilize phosphorylation as a tool to demonstrate if """"""""mixed"""""""" channels (heteromeric, mono-heteromeric) gate or have unitary conductances which are significantly different from homotypic channel types.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063969-03
Application #
6537727
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Wang, Lan-Hsiang
Project Start
2000-09-27
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$298,000
Indirect Cost

  Institution

Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202

  Publications

Garciarena, Carolina D; Malik, Akif; Swietach, Pawel et al. (2018) Distinct moieties underlie biphasic H+ gating of connexin43 channels, producing a pH optimum for intercellular communication. FASEB J 32:1969-1981
Mondal, Abhijit; Appadurai, Daniel A; Akoum, Nazem W et al. (2017) Computational simulations of asymmetric fluxes of large molecules through gap junction channel pores. J Theor Biol 412:61-73
Kozoriz, Michael G; Bechberger, John F; Bechberger, Geralyn R et al. (2010) The connexin43 C-terminal region mediates neuroprotection during stroke. J Neuropathol Exp Neurol 69:196-206
Sachse, Frank B; Moreno, A P; Seemann, G et al. (2009) A model of electrical conduction in cardiac tissue including fibroblasts. Ann Biomed Eng 37:874-89
Sachse, Frank B; Moreno, Alonso P; Abildskov, J A (2008) Electrophysiological modeling of fibroblasts and their interaction with myocytes. Ann Biomed Eng 36:41-56
Moreno, Alonso P; Lau, Alan F (2007) Gap junction channel gating modulated through protein phosphorylation. Prog Biophys Mol Biol 94:107-19
Shen, Yongquan; Khusial, P Raaj; Li, Xun et al. (2007) SRC utilizes Cas to block gap junctional communication mediated by connexin43. J Biol Chem 282:18914-21
Moreno, Alonso P; Berthoud, Viviana M; Perez-Palacios, Gregorio et al. (2005) Biophysical evidence that connexin-36 forms functional gap junction channels between pancreatic mouse beta-cells. Am J Physiol Endocrinol Metab 288:E948-56
Zhong, G; Mantel, P L; Jiang, X et al. (2003) LacSwitch II regulation of connexin43 cDNA expression enables gap-junction single-channel analysis. Biotechniques 34:1034-9, 1041-4, 1046
Martinez, Agustin D; Hayrapetyan, Volodya; Moreno, Alonso P et al. (2002) Connexin43 and connexin45 form heteromeric gap junction channels in which individual components determine permeability and regulation. Circ Res 90:1100-7

Showing the most recent 10 out of 12 publications