Characterization of the Hyperpolarization-Activated Current, I _f , in Ventricular Myocytes From Human Failing Heart

Abstract

I(f) is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that I(f) could be an arrhythmogenic mechanism in patients with severe heart failure.

Dominant-Negative Suppression of HCN Channels Markedly Reduces the Native Pacemaker Current I f and Undermines Spontaneous Beating of Neonatal Cardiomyocytes

“…In any event, our HCN constructs may prove useful to further determine the physiological role of I f and HCN channels for cardiac pacing in the sinoatrial node and for arrhythmogenesis in diseased adult ventricular myocardium. [1][2][3] Detailed molecular insight into the contribution of this diastolic current to cardiac pacing might facilitate the rational design of blockers or activator drugs and of gene therapy strategies to modify cardiac automaticity.…”

“…In pacemaker regions and spontaneously beating neonatal cardiocytes, I f is believed to contribute physiologically to spontaneous diastolic depolarization, whereas in diseased ventricular myocardium, this current might play a role in arrhythmogenesis. [1][2][3] However, whether I f is essential for pacemaker activity or instead modulates the beating frequency of autonomic myocardial cells has been controversial over the years. 4 -7 Four HCN gene family members have been cloned, 3 of which are present in heart (HCN1, HCN2, and HCN4), with varying message levels in different cardiac regions.…”

La découverte de l’ivabradine (Procoralan®), inhibiteur sélectif du courantpacemakerIf: Une nouvelle approche thérapeutique des cardiopathies ischémiques

“…Par ailleurs, le courant I f , normalement seulement détectable au niveau du tissu nodal, peut être exprimé au niveau de cellules ventriculaires de coeurs en insuffisance cardiaque [53] où il pourrait représenter un mécanisme arythmogène dont l'inhibition par ivabradine pourrait être bénéfique. Enfin, le défi majeur pour l'ivabradine est de démontrer, par les grands essais cliniques en cours, sa capacité à améliorer le pronostic des cardiopathies ischémiques en réduisant la mortalité et la survenue d'événements cardiovasculaires majeurs, en prévenant l'ischémie myocardique, en limitant la progression et les complications de l'athérosclérose, en renforçant le développement de la circulation coronaire collaté-rale, en améliorant le remodelage cardiaque et en inhibant certains mécanismes arythmogènes.…”

Developmental changes in functional expression and β-adrenergic regulation of If in the heart of mouse embryo

“…Maybe, only the cells of heart conduction system had been collected with the procedure they used, so there is some differences from atrial and ventricular myocytes. I ƒ is re-expressed in the adult ventricular myocytes isolated from heart failure and hypotrophy [11], [13], [23], therefore the automatic rhythmicity may reappear in these ventricular myocytes and the re-exp r e s s i o n o f I ƒ m a y h a v e r e l e v a n c e w i t h arrhythmogenesis in these heart diseases [17], [24]. Therefore, our research on I ƒ in the embryonic mouse heart is also useful to study pathophysiological phenomena of heart failure and hypertrophy.…”

“…It is well known that hypertrophy induces a re-expression of genes encoding fetal proteins [11], therefore the currents exist during the fetal life may occur in pathological heart. In fact, I ƒ is present in ventricular myocytes of hypertensive rat [12] as well as recently in human failing heart [13]. The presence of I ƒ in ventricular myocytes may have relevance with arrhythmogenesis in hypertrophy and heart failure [28].…”