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Gap junction intercellular communication pathways in normal and diseased human ventricular myocardium

Peters, Nicholas S.; (1994) Gap junction intercellular communication pathways in normal and diseased human ventricular myocardium. Doctoral thesis (M.D), UCL (University College London). Green open access

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The gap junction is the plasma membrane specialisation responsible for electrical and chemical coupling of cardiac myocytes. Despite increasingly recognised significance, there is a paucity of data on gap junctions in the human heart. This thesis reports studies in which confocal microscopic immunohistochemistry of the principal gap-junctional protein, connexin43, and electron microscopy, were used to characterise gap-junctional organisation in developing and adult human ventricular myocardium, and to investigate altered gap-junctional organisation as a possible contributing factor to electromechanical dysfunction in congenital, ischaemic and hypertrophic myocardial diseases. In the adult left ventricle, connexin43-gap junctions occupy a surface area of 0.0051 μm2/μm3 myocardial volume, and are confined to the intercalated disks. In the neonate, connexin43-gap junctions are distributed over the entire surface of ventricular myocytes, with a progressive (linear) change to the adult pattern by six years of age. Recurrently ischaemic adult ventricular myocardium has gap junctions confined to intercalated disks of normal number and appearance, but with a reduced gap-junctional surface area (0.0027 μm2/μm3), as also found in chronically hypertrophied ventricular myocardium (0.0031 μm2/μm3). When expressed per myocyte, there is a 30% reduction in gap-junctional content in ischaemic ventricle compared with normal. The pattern of junction distribution is grossly disturbed at the surviving borders of myocardial infarcts, both early and after healing. In the early hypertrophic response to acute renovascular hypertension in an animal model, left ventricular myocytes show a 35% increase in gap- junctional surface area per unit myocyte volume. Hearts with congenitally anomalous morphology are not associated with abnormal gap junction distribution. The cells comprising accessory atrioventricular pathways have a junction distribution suggestive of ventricular myocytes, and of efficient coupling, despite vestigial contractile apparatus. Although the pattern of myocardial gap junction distribution is severely disrupted at infarct borders, the site of origin of many clinical arrhythmias, there are no widespread disturbances of gap-junctional distribution patterns, in the diseases investigated. Quantitative alterations of gap-junctional expression, however, may be a hitherto unrecognised determinant of mechanical and arrhythmic dysfunction in diseased hearts.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Gap junction intercellular communication pathways in normal and diseased human ventricular myocardium
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10105985
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