Circulation Research. 2002;91:104-111
Published online before print June 13, 2002, doi: 10.1161/01.RES.0000025638.24255.AA
Published online before print June 13, 2002, doi: 10.1161/01.RES.0000025638.24255.AA
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© 2002 American Heart Association, Inc.
Molecular Medicine |
Cardiac Gap Junction Channels Show Quantitative Differences in Selectivity
From the Department of Physiology and Biophysics (V.V., P.R.B.), State University of New York at Stony Brook, Stony Brook, NY; and the Department of Pediatrics (E.C.B.), Section of Hematology/Oncology, University of Chicago, Chicago, Ill. V.V. is on leave from the Institute for Biomedical Research, Kaunas Medical University, Kaunas, Lithuania.
Correspondence to Peter R. Brink, Dept of Physiology and Biophysics, SUNY at Stony Brook, Stony Brook, NY 11794. E-mail peter{at}mail.pnb.sunysb.edu
Several proteins including connexin40 (Cx40) and connexin43 (Cx43) form gap junctions between cells of the heart; they may be found separately or may be coexpressed. These connexins form channels with differing conductance and permeability properties. Cx40 and Cx43 are each required for normal electrical conduction between cells in different regions of the heart. We hypothesized that the major difference between these connexins might be in their selective intercellular passage of small molecules such as second messengers, which can be assessed using biologically inert fluorescent probes. Therefore, we designed experimental paradigms to quantitate the permeability properties of these cardiac connexins using simultaneous measurement of junctional conductance (gj) by the double whole-cell patch-clamp technique and intercellular transfer of Lucifer Yellow (LY) by fluorescence microscopy. These studies were performed in HeLa cells stably transfected with Cx40 or Cx43 or cotransfected with both connexins. We found that homotypic Cx43 channels were about 5 times more permeable to LY than homotypic Cx40 channels (flux of 
1560 versus 300 molecules/channel per second). Channels between heterotypic (Cx40-Cx43) cell pairs and between pairs of coexpressing cells exhibited intermediate LY permeability. The permeability ratio for LY relative to monovalent cation (K+) ranged from 0.0025 for Cx40 to 0.028 for Cx43. These permeability ratios suggest that the connexins are highly selective for solutes in the size and charge range of many second messengers. Moreover, the data indicate that coexpression of connexins does not generate unique permeability characteristics, but rather results in an intermediate permeability for solutes involved in metabolic/biochemical coupling.
Key Words: connexin40 • connexin43 • electrophysiology • gap junction • permselectivity
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