[Long QT syndrome: from clinical discovery to molecular etiopathogenesis].
Before the era of Molecular Biology the etiopathogenic mechanism of the long QT Syndrome (LQTS) was hypothetized to be an inhomogeneity in the innervation of the myocardium by the sympathetic system resulting in abnormal myocardial repolarisation, prolongation of the QT interval and various rhythm disorders. The progress of Molecular Biology has led to abandon this hypothesis; it is now agreed that the etiopathology of the various forms of the LQTS and of the arrythmias which are associated with it lies in the presence of mutations localized on genes coding either for cardio-specific ionic channels or for proteins which modulate the activity of these ionic channels. Thus, the alterations, direct or indirect, of these cardio-specific ionic channels lead to a delayed repolarization of myocardial cells which manifest itself on the electrocardiogram by a prolongation of the QT interval. This delayed repolarization of myocardial cells would induce a reactivation of myocardial ionic channels of the L-Ca++ type which leads to the development of secondary late depolarization which represent the underlying cellular mechanisms for "torsade de pointes". This hypothesis is experimentally reinforced by the observation both in animals and in men of a prolongation of the QT interval as well as aspecific tachyarrythmias after pharmacologic blockade of myocardial potassium channels. Therefore the long QT syndromes probably find their origin in genetic abnormalities of the electro-ionic system of the heart whereas the mechanical function and the autonomic innervation appear to be entirely normal.
Czajkowski
V
V
Service de Cardiologie, Université de Liège.
Kulbertus
H
H
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008133:Long QT Syndrome / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics; D011506:Proteins / Q000235:genetics; D013564:Sympathetic Nervous System / Q000503:physiopathology; D016171:Torsades de Pointes / Q000209:etiology / Q000235:genetics
D015220:Calcium Channels; D007473:Ion Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011506:Proteins
Le syndrome du QT long: de la découverte clinique à l'étiopathogénie moléculaire.