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000061425 0247_ $$2DOI$$a10.1038/emboj.2008.3
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000061425 041__ $$aeng
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000061425 084__ $$2WoS$$aBiochemistry & Molecular Biology
000061425 084__ $$2WoS$$aCell Biology
000061425 1001_ $$0P:(DE-Juel1)VDB28136$$aHarzheim, D.$$b0$$uFZJ
000061425 245__ $$aCardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP
000061425 260__ $$aLondon [u.a.]$$bNature Publishing Group$$c2008
000061425 300__ $$a692 - 703
000061425 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000061425 440_0 $$01793$$aEmbo Journal$$v27$$x0261-4189
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000061425 520__ $$aImportant targets for cAMP signalling in the heart are hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels that underlie the depolarizing 'pacemaker' current, I(f). We studied the role of I(f) in mice, in which binding of cAMP to HCN4 channels was abolished by a single amino-acid exchange (R669Q). Homozygous HCN4(R669Q/R669Q) mice die during embryonic development. Prior to E12, homozygous and heterozygous embryos display reduced heart rates and show no or attenuated responses to catecholaminergic stimulation. Adult heterozygous mice display normal heart rates at rest and during exercise. However, following beta-adrenergic stimulation, hearts exhibit pauses and sino-atrial node block. Our results demonstrate that in the embryo, HCN4 is a true cardiac pacemaker and elevation of HCN4 channel activity by cAMP is essential for viability. In adult mice, an important function of HCN4 channels is to prevent sinus pauses during and after stress while their role as a pacemaker of the murine heart is put into question. Most importantly, our results indicate that HCN4 channels can fulfil their physiological function only when cAMP is bound.
000061425 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems$$cP33$$x0
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000061425 650_2 $$2MeSH$$aAnimals
000061425 650_2 $$2MeSH$$aCells, Cultured
000061425 650_2 $$2MeSH$$aCyclic AMP: physiology
000061425 650_2 $$2MeSH$$aCyclic Nucleotide-Gated Cation Channels: genetics
000061425 650_2 $$2MeSH$$aCyclic Nucleotide-Gated Cation Channels: physiology
000061425 650_2 $$2MeSH$$aEmbryonic Development: physiology
000061425 650_2 $$2MeSH$$aFemale
000061425 650_2 $$2MeSH$$aHeart: physiology
000061425 650_2 $$2MeSH$$aHeart Rate
000061425 650_2 $$2MeSH$$aMice
000061425 650_2 $$2MeSH$$aMice, Inbred C57BL
000061425 650_2 $$2MeSH$$aMice, Transgenic
000061425 650_2 $$2MeSH$$aMutation
000061425 650_2 $$2MeSH$$aMyocytes, Cardiac: physiology
000061425 650_2 $$2MeSH$$aPregnancy
000061425 650_7 $$00$$2NLM Chemicals$$aCyclic Nucleotide-Gated Cation Channels
000061425 650_7 $$00$$2NLM Chemicals$$aHCN3 protein, mouse
000061425 650_7 $$060-92-4$$2NLM Chemicals$$aCyclic AMP
000061425 650_7 $$2WoSType$$aJ
000061425 65320 $$2Author$$acardiology
000061425 65320 $$2Author$$acyclic nucleotides
000061425 65320 $$2Author$$aheart
000061425 65320 $$2Author$$aion channel
000061425 65320 $$2Author$$asignalling
000061425 7001_ $$0P:(DE-Juel1)VDB74441$$aPfeiffer, K.H.$$b1$$uFZJ
000061425 7001_ $$0P:(DE-HGF)0$$aFabritz, L.$$b2
000061425 7001_ $$0P:(DE-HGF)0$$aKremmer, E.$$b3
000061425 7001_ $$0P:(DE-HGF)0$$aBuch, T.$$b4
000061425 7001_ $$0P:(DE-HGF)0$$aWaisman, A.$$b5
000061425 7001_ $$0P:(DE-HGF)0$$aKirchhof, P.$$b6
000061425 7001_ $$0P:(DE-Juel1)VDB728$$aKaupp, U. B.$$b7$$uFZJ
000061425 7001_ $$0P:(DE-Juel1)VDB1505$$aSeifert, R.$$b8$$uFZJ
000061425 773__ $$0PERI:(DE-600)1467419-1$$a10.1038/emboj.2008.3$$gVol. 27, p. 692 - 703$$p692 - 703$$q27<692 - 703$$tThe @EMBO journal online$$v27$$x0261-4189$$y2008
000061425 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262033
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000061425 9201_ $$0I:(DE-Juel1)VDB804$$d31.12.2008$$gINB$$kINB-1$$lZelluläre Biophysik$$x0
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