Expression of the hyperpolarization-activated current, If, in cultured adult rat ventricular cardiomyocytes and its modulation by hypertrophic factors

Stillitano, Francesca; Sartiani, Laura; DePaoli, Petra; Mugelli, Alessandro; Cerbai, Elisabetta

doi:10.1016/j.phrs.2007.12.002

Cited by 15 publications

(9 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although hyperpolarization may be beneficial in that it may prevent arrhythmias, it could also trigger I f /I h . I f /I h is typically a Na ϩ /K ϩ inward current associated with hyperpolarization-activated cyclic nucleotide-gated channels, playing a pivotal role in cardiac pacemaking but associated with cardiac hypertrophy and failure when expressed in the ventricles (76). LPI has been shown to have GPR55-independent hyperpolarizing effects on the endothelial cell membrane (77).…”

Section: Discussionmentioning

confidence: 99%

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Deliu²,

Zhang

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The LPI-sensitive receptor GPR55 signals through Ca 2ϩ . Results: Activation of sarcolemmal versus intracellular GPR55 mobilizes Ca 2ϩ from distinct pools and associates with cardiomyocyte depolarization and hyperpolarization, respectively. Conclusion: GPR55 location critically affects LPI-induced modulation of cardiomyocyte function. Significance: We identify GPR55 as a new receptor regulating cardiac function at two cellular sites.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Deliu²,

Zhang

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…However, it must be recalled that f-channels result from assembling of different isoforms, and the exact stoichiometry is unknown; although the expression of HCN1 and HCN3 in rat ventricular myocytes seems to be very low or undetectable, 41 we cannot exclude the contribution of other isoforms to the persistent upregulation of I f . Furthermore, a posttranscriptional regulation of HCN by microRNA (miR) has been shown 42 that may at least partially account for changes in I f density during development.…”

Section: Limitations Of the Study And Clinical Implicationsmentioning

confidence: 94%

Prenatal exposure to carbon monoxide delays postnatal cardiac maturation

Sartiani

Stillitano

Luceri

et al. 2010

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

Prenatal exposure to toxicants, such as maternal smoking, may impair cardiovascular autonomic maturation in infants. We recently showed that exposure of pregnant rats to a mild concentration of carbon monoxide (CO), a component of cigarette smoke, delays postnatal electrophysiological maturation of ventricular myocytes from newborns rats, likely predisposing to life-threatening arrhythmias. To get a comprehensive view of developmental molecular abnormalities induced, at cardiac level, by prenatal CO exposure, we used microarray analysis approach on the rat heart at 4, 7 and 20 days postnatal life. The relationship between molecular and functional alterations was investigated by assessing the ventricular expression of f-current, an electrophysiological marker of immature cardiac phenotype. Rats were prenatally exposed to 0 (CTR) or 150 p.p.m. CO and mRNA obtained from ventricular samples. Differential analysis and biological pathway analysis of microarray data were performed by using Newton's approach and the GENMAPP/MAPPFinder, respectively. The real-time RT-PCR reactions were performed by TaqMan probe-based chemistry. Freshly isolated patch-clamped ventricular cardiomyocytes were used to measure I f . Genes and pathways controlling cell cycle and excitation-contraction coupling were significantly modified in CO-exposed rats. The higher effect was observed in cardiomyocytes harvested from 7-day-old rats, in which mRNA expression for crucial sarcomeric proteins (myosin and actin subunits, troponin I), transporters (Ca 2 þ transporting ATPase) and enzymes (aldolase) were significantly downregulated. Accordingly, the molecular and functional expression of f-channels, which represents a marker of fetal ventricular phenotype, was transiently greater in CO-exposed rats ( þ 200%) than in control ones. In conclusion, our study provides new insights into the molecular and functional mechanisms underlying cardiac maturation and its impairment by prenatal exposure to toxic components of smoking, such as CO.

show abstract

“…Interestingly however, I f expression is strongly upregulated in pathological conditions, and more specifically in cardiac hypertrophy and heart failure [37] [40] [41] [42]. The increase in I f expression, mainly due to HCN2 (and HCN4) upregulation, may lead to increased spontaneous cellular activity and thus contribute to ectopic rhythm [43], again supporting a correlation between f-channel expression and pacing.…”

Section: Point: Difrancescomentioning

confidence: 99%

What keeps us ticking: a funny current, a calcium clock, or both?

Lakatta

DiFrancesco²

2009

Journal of Molecular and Cellular Cardiology

261

257

View full text Add to dashboard Cite

Prologue The processes underlying the initiation of the heartbeat, whether due to intracellular metabolism or surface membrane events, have always been a major focus of cardiac research. About 50 years ago, pioneering work initiated by Silvio Weidmann and others applied the Hodgkin-Huxley formalism of membrane excitation to interpret the cardiac electrical activity, including the pacemaker depolarization (see D. Noble, 1979 The initiation of the heartbeat, Clarendon Press). The underlying idea was that voltage- and time-dependent gating of various surface membrane channels not only generated the cardiac pacemaker action potential (AP), but also controlled the spontaneous depolarization between AP’s and thus determined when the next AP would occur. According to this description, the ensemble of surface membrane ion channels works as a clock that regulates the rate and rhythm of spontaneous AP firing, otherwise known as normal automaticity. A formidable research effort then concentrated in attempting to target which of the surface membrane ion channels had an important role in controlling the spontaneous diastolic depolarization (DD). Originally, a major role was attributed to the “IK-decay theory”. This was strongly influenced by the previous Hodgkin-Huxley model of nerve AP, which described the slow depolarization following a nerve AP as due to the decay of a K+ current. This model of pacemaker depolarization lasted some 20 years, until it was turned upside-down by a full re-interpretation based on the discovery of the If current. Other ionic currents gated by membrane depolarization, i.e. ICaL, ICaT, IST, non-gated and non-specific background leak currents, and also a current generated by the Na-Ca exchange (NCX) carrier, were also proposed to be involved in pacemaking. Based on a wealth of experimental evidence, If is today considered as the most important ion channel involved in the rate regulation of cardiac pacemaker cells, and is sometimes referred to as “the pacemaker channel.” Several studies, some of which recent, have also shown that in addition to voltage and time, surface membrane electrogenic molecules are strongly modulated by Ca2+ and phosphorylation. The studies of a sub-group of pacemaker cell researchers focusing upon intracellular Ca2+ movements in pacemaker cells spawned the idea that intracellular Ca2+ is an important player in controlling pacemaker cell automaticity. This elevated the status of NCX current as a major Ca2+-activated electrogenic mechanism. But the fine details of intracellular Ca2+ movements, specifically those beneath the cell membrane during DD, were not at hand, and the concept of Ca2+ involvement in pacemaking stalled, whilst the concept of If control continued to soar—expanding to the design of novel drug development and biological pacemakers. More recent discoveries over the past decade, made possible by simultaneous submembrane Ca2+ imaging and membrane potential or current recordings with cell-attached patch electrodes, have shown that critically timed Ca2+ releases ...

show abstract

Expression of the hyperpolarization-activated current, If, in cultured adult rat ventricular cardiomyocytes and its modulation by hypertrophic factors

Cited by 15 publications

References 44 publications

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Differential Activation of Cultured Neonatal Cardiomyocytes by Plasmalemmal Versus Intracellular G Protein-coupled Receptor 55

Prenatal exposure to carbon monoxide delays postnatal cardiac maturation

What keeps us ticking: a funny current, a calcium clock, or both?

Contact Info

Product

Resources

About