CLINICAL STUDY
Relative expression of immunolocalized connexins 40 and 43 correlates with human atrial conduction properties
Prapa Kanagaratnam, MRCP* ,
Stephen Rothery, BSc*,
Pravina Patel, BSc*,
Nicholas J. Severs, DSc* and
Nicholas S. Peters, MD, FRCP*,*
* Heart and Lung Division of Imperial College School of Medicine, London, United Kingdom
St. Mary’s Hospital, London, United Kingdom
Manuscript received April 13, 2001;
revised manuscript received September 10, 2001,
accepted September 20, 2001.
* Reprint requests and correspondence: Prof. Nicholas S. Peters, Department of Cardiology, St. Mary’s Hospital, Praed Street, London W2 1NY, United Kingdom.
n.peters{at}ic.ac.uk
OBJECTIVES: The aim of this study was to determine the relationship between immunolocalized gap-junctional proteins and human atrial conduction.
BACKGROUND: As a determinant of intercellular conductance, gap-junctional coupling is considered to influence myocardial conduction velocity. This study tested the hypothesis that the quantity of immunodetectable atrial gap-junctional proteins, connexin40 (Cx40) and connexin43 (Cx43), are related to atrial conduction velocity in humans.
METHODS: Epicardial mapping was performed on 16 patients undergoing cardiac surgery using an array of 56 unipolar electrodes. The conduction velocity was measured over the right atrial free wall during sinus rhythm and at a paced cycle length 500 ms. A biopsy from this region was excised for quantitative confocal immunodetection of Cx40 and Cx43.
RESULTS: There was no correlation between conduction velocity and Cx43 signal or total connexin signal (Cx40 + Cx43). Connexin40 signal was inversely correlated with conduction velocity (p = 0.036). However, the relative quantity of connexin immunolabeling (expressed as Cx40/[Cx40+Cx43] or the inverse equivalent Cx43/[Cx40+Cx43]) was strongly associated with conduction velocity during sinus rhythm, such that, as the proportion of Cx40 signal increased (and that for Cx43 decreased), the conduction velocity decreased (p < 0.005, r = –0.66). Furthermore, with paced atrial activation at 500 ms cycle length, the relative quantity of connexin labeling (Cx40/[Cx40+Cx43]) correlated with the rate-related change in atrial conduction velocity (p < 0.02, r = 0.59).
CONCLUSIONS: In human right atrium, conduction velocity is inversely related to immunodetectable Cx40 levels. The relative level of connexins 40 and 43 signal is strongly associated with atrial conduction properties, suggesting that interactions between the two connexins may result in novel coupling properties.
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Abbreviations and Acronyms
| | BSA | | bovine serum albumin | | Cx40 | | connexin40 | | Cx43 | | connexin43 | | FITC | | fluorescein isothiocyanate | | PBS | | phosphate-buffered saline | | TRITC | | tetramethyl rhodamine isothiocyanate |
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