Circulation Research. 2003
Published online before print January 30, 2003, doi: 10.1161/01.RES.0000059301.81035.06
Published online before print January 30, 2003, doi: 10.1161/01.RES.0000059301.81035.06
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Submitted on August 13, 2002
Revised on January 22, 2003
Accepted on January 22, 2003
Remodeling of Gap Junctional Channel Function in Epicardial Border Zone of Healing Canine Infarcts
Jian-An Yao *;
From the Department of Pharmacology and Center for Molecular Therapeutics (J.-A.Y., P.A.B., A.L.W.), Columbia University, New York, NY; and Imperial College and St Mary's Hospital (P.P., W.H., N.S.P.), London, UK.
* To whom correspondence should be addressed. E-mail: jy18{at}columbia.edu.
The epicardial border zone (EBZ) of canine infarcts has increased anisotropy because of transverse conduction slowing. It remains unknown whether changes in gap junctional conductance (Gj) accompany the increased anisotropy. Ventricular cell pairs were isolated from EBZ and normal hearts (NZ). Dual patch clamp was used to quantify Gj. At a transjunctional voltage (Vj) of +10 mV, side-to-side Gj of EBZ pairs (9.2±3.4 nS, n=16) was reduced compared with NZ side-to-side Gj (109.4±23.6 nS, n=14, P<0.001). Gj of end-to-end coupled cells was not reduced in EBZ. Steady-state Gj of both NZ and EBZ showed voltage dependence, described by a two-way Boltzmann function. Half-maximal activation voltage in EBZ was shifted to higher Vj in positive and negative directions. Immunoconfocal planimetry and quantification showed no change in connexin43 per unit cell volume or surface area in EBZ. Decreased side-to-side coupling occurs in EBZ myocytes, independent of reduced connexin43 expression, and is hypothesized to contribute to increased anisotropy and reentrant arrhythmias.
Key words: gap junction • myocardial infarction • arrhythmias
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