Transcription profiling of HCN-channel isotypes throughout mouse cardiac development

Schweizer, Patrick; Yampolsky, Pessah; Malik, Rizwan; Thomas, Dierk; Zehelein, Joerg; Katus, Hugo A.; Koenen, Michael

doi:10.1007/s00395-009-0031-5

Cited by 57 publications

(40 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A minority of myocytes isolated from the hearts of adult rats express I f , which, when present, was of small amplitude. In accordance with data reported in the fetal mouse (Yasui et al, 2001;Mommersteeg et al, 2007;Schweizer et al, 2009), expression analysis in the rat documented that both HCN4 and HCN2 isoforms account for the majority of total HCN transcript in the neonatal ventricle, while HCN1 and HCN3 isoforms are not expressed at detectable levels . Interestingly, HCN4 is down-regulated during rat heart maturation, but in association with HCN2 it undergoes a clear-cut up-regulation after cardiac infarction (Suffredini et al, 2009).…”

Section: Funny Channel Over-expression In Cardiomyocytes Is a Marker supporting

confidence: 89%

The Funny Current in Cardiac Non-Pacemaker Cells: Functional Role and Pharmacological Modulation

Sartiani¹,

Cerbai²,

Mugelli³

2011

Modern Pacemakers - Present and Future

View full text Add to dashboard Cite

Section: Funny Channel Over-expression In Cardiomyocytes Is a Marker supporting

confidence: 89%

The Funny Current in Cardiac Non-Pacemaker Cells: Functional Role and Pharmacological Modulation

Sartiani¹,

Cerbai²,

Mugelli³

2011

Modern Pacemakers - Present and Future

View full text Add to dashboard Cite

“…MiRP-1 is a b-subunit that enhances the expression and speeds up the kinetics of activation of the HCN-derived proteins; in the adult heart, MiRP-1 is expressed in the sinus node region but hardly detectable in the ventricle. 16 HCN2, whose density has been reported to increase in postnatal ventricular maturation with a peak between 10 and 20 days of age, 17 was significantly less expressed in CO-treated vs Ctr hearts at 7 (0.53 ± 0.06 vs 1.08 ± 0.2) and 28 (0.72 ± 0.07 vs 1.02 ± 0.001) days (Figure 5b). …”

Section: Molecular Properties Of F-channels In Co-exposed Neonatal Ratsmentioning

confidence: 85%

Prenatal exposure to carbon monoxide delays postnatal cardiac maturation

Sartiani

Stillitano

Luceri

et al. 2010

Laboratory Investigation

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

“…HCN4 becomes dominant in association with the onset of cardiac contractions (Qu et al, 2008;Schweizer et al, 2009). While we are not prescribing Lamarkian recapitulation of phylogeny, the similarity points to a functional role of variations in cardiac HCN isoform expression.…”

Section: Discussionmentioning

confidence: 99%

Phylogeny and effects of anoxia on hyperpolarization-activated, cyclic nucleotide-gated channel gene expression in the heart of a primitive chordate, the Pacific Hagfish (eptatretus stoutii)

Wilson

Stecyk

Couturier

et al. 2013

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYThe aneural heart of the Pacific hagfish, Eptatretus stoutii, varies heart rate fourfold during recovery from anoxia. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play an important role in establishing the pacemaker rate of vertebrate hearts, were postulated to be present in this ancestral vertebrate heart, and it was also theorized that changes in hagfish heart rate with oxygen availability involved altered HCN expression. Partial gene cloning revealed six HCN isoforms in the hagfish heart. Hagfish representatives of HCN2, HCN3 and HCN4 were discovered, with HCN2 and HCN3 existing as isoforms designated as HCN2a, HCN2b, HCN3a, two paralogs of HCN3b, and HCN3c. Phylogenetic analysis revealed HCN3b and HCN3c to be ancestral, followed by HCN3a, HCN4 and HCN2. Moreover, HCN3a expression was dominant in both the atrial and ventricular chambers, suggesting that the HCN4 dominance in adult mammalian hearts appeared after hagfish divergence. HCN expression was higher in the atrium than in the ventricle, as might be expected given that atrial beating rate is known to be faster than the ventricular rate. In addition, mRNA expression under normoxic conditions was compared with that following 24 h of anoxia, and either a 2-h or 36-h recovery in normoxic water. In the ventricle, anoxia decreased HCN3a but not HCN4 expression. In contrast, atrial HCN3a expression significantly increased following 2 h of recovery, before returning to control levels following 36 h of recovery, possibly contributing to heart rate changes previously observed under these conditions.

show abstract

Transcription profiling of HCN-channel isotypes throughout mouse cardiac development

Cited by 57 publications

References 41 publications

The Funny Current in Cardiac Non-Pacemaker Cells: Functional Role and Pharmacological Modulation

The Funny Current in Cardiac Non-Pacemaker Cells: Functional Role and Pharmacological Modulation

Prenatal exposure to carbon monoxide delays postnatal cardiac maturation

Phylogeny and effects of anoxia on hyperpolarization-activated, cyclic nucleotide-gated channel gene expression in the heart of a primitive chordate, the Pacific Hagfish (eptatretus stoutii)

Contact Info

Product

Resources

About