Regulation of gap junctional charge selectivity in cells coexpressing connexin 40 and connexin 43

Department of Physiology, University of Arizona, Tucson, Arizona Submitted 24 March 2009 ; accepted in final form 20 May 2009 Expression of connexin 40 (Cx40) and Cx43 in cardiovascular tissues varies as a function of age, injury, and development with unknown consequences on the selectivity of junct...

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Published in:American journal of physiology. Heart and circulatory physiology 2009-07, Vol.297 (1), p.H450-H459
Main Authors: Heyman, Nathanael S, Kurjiaka, David T, Ek Vitorin, Jose F, Burt, Janis M
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cardiovascular system
Cells
Connexin 43 - biosynthesis
Connexin 43 - physiology
Connexins - biosynthesis
Connexins - physiology
Data Interpretation, Statistical
Electrophoretic Mobility Shift Assay
Electrophysiology
Enzyme Activation - drug effects
Gap Junction alpha-5 Protein
Gap Junctions - physiology
Kinetics
Patch-Clamp Techniques
Permeability
Phosphorylation
Protein Kinase C - metabolism
Rats
Tetradecanoylphorbol Acetate - pharmacology
Tissues
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Summary:Department of Physiology, University of Arizona, Tucson, Arizona Submitted 24 March 2009 ; accepted in final form 20 May 2009 Expression of connexin 40 (Cx40) and Cx43 in cardiovascular tissues varies as a function of age, injury, and development with unknown consequences on the selectivity of junctional communication and its acute regulation. We investigated the PKC-dependent regulation of charge selectivity in junctions composed of Cx43, Cx40, or both by simultaneous assessment of junctional permeance rate constants (B dye ) for dyes of similar size but opposite charge, N , N , N -trimethyl-2-[methyl-(7-nitro-2,1,3-benzoxadiol-4-yl)amino]ethanaminium (NBD-M-TMA; +1) and Alexa 350 (–1). The ratio of dye rate constants (B NBD-M-TMA /B Alexa 350 ) indicated that Cx40 junctions are cation selective (10.7 ± 0.5), whereas Cx43 junction are nonselective (1.22 ± 0.14). In coexpressing cells, a broad range of junctional selectivities was observed with mean cation selectivity increasing as the Cx40 to Cx43 expression ratio increased. PKC activation reduced or eliminated dye permeability of Cx43 junctions without altering their charge selectivity, had no effect on either permeability or charge selectivity of Cx40 junctions, and significantly increased the cation selectivity of junctions formed by coexpressing cells (approaching charge selectivity of Cx40 junctions). Junctions composed of Cx43 truncated at residue 257 (Cx43tr) were also not charge selective, but when Cx43tr was coexpressed with Cx40, a broad range of junctional selectivities that was unaffected by PKC activation was observed. Thus, whereas the charge selectivities of homomeric/homotypic Cx43 and Cx40 junctions appear invariant, the selectivities of junctions formed by cells coexpressing Cx40 and Cx43 vary considerably, reflecting both their relative expression levels and phosphorylation-dependent regulation. Such regulation could represent a mechanism by which coexpressing cells such as vascular endothelium and atrial cells regulate acutely the selective intercellular communication mediated by their gap junctions. heteromeric channel; homomeric channel; carboxy-terminal domain; PKC-dependent regulation Address for reprint requests and other correspondence: J. M. Burt, Dept. of Physiology, Univ. of Arizona, PO Box 245051, Tucson, AZ 85724 (e-mail: jburt{at}u.arizona.edu )
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00287.2009