Published online before print September 18, 2003, doi: 10.1161/01.RES.0000095977.66660.86
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Submitted on May 9, 2003
Revised on August 29, 2003
Accepted on September 5, 2003
Cell Coupling Between Ventricular Myocyte Pairs From Connexin43-Deficient Murine Hearts
Jian-An Yao ;
From the Department of Pharmacology and Center for Molecular Therapeutics (J.-A.Y., A.L.W.), College of Physicians and Surgeons, Columbia University, New York, NY; The Leon H. Charney Division of Cardiology, Department of Medicine (D.E.G., F.L., G.I.F.), New York University School of Medicine, New York, NY.
* To whom correspondence should be addressed. E-mail: alw4{at}columbia.edu.
Mice with cardiac-restricted inactivation of the connexin43 gene (CKO mice) have moderate slowing of ventricular conduction and lethal arrhythmias. Mechanisms through which propagation is maintained in the absence of Cx43 are unknown. We, evaluated gap junctional conductance in CKO ventricular pairs, using dual patch clamp methods. Junctional coupling was reduced to 4±2 nS (side-to-side) and 11±2 nS (end-to-end), including 21% of cell-pairs with no detectable coupling, compared with 588±104 nS (side-to-side) and 558±92 nS (end-to-end) in control cell-pairs. Voltage dependence of control gap junctions was characteristic of Cx43. CKO conductance showed increased voltage dependence, suggesting low-level expression of other connexin isoforms. From theoretical models, this degree of CKO coupling is not expected to support levels of conduction persisting in vivo, suggesting the possibility that there are additional mechanisms for maintained propagation when gap junctional conductance is severely reduced.
Key words: gap junctions • connexin • remodeling • arrhythmias
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