Dominant-negative suppression of HCN channels markedly reduces the native pacemaker current If and undermines spontaneous beating of neonatal cardiomyocytes

Circulation

Volumn 107, Issue 3, 2003, Pages 485-489

  Er, Fikret ^a   Larbig, Robert ^a   Ludwig, Andreas ^b   Biel, Martin ^b   Hofmann, Franz ^b   Beuckelmann, Dirk J ^a   Hoppe, Uta C ^a  

^a UNIVERSITY OF COLOGNE   (Germany)

^b NONE

Author keywords

Electrophysiology; Gene therapy; Ion channels; Pacemakers; Viruses

Indexed keywords

ADENOVIRUS VECTOR; ION CHANNEL; PROTEIN; PROTEIN HCN; PROTEIN HCN2; PROTEIN HCN4; UNCLASSIFIED DRUG;

ACTION POTENTIAL; ANIMAL CELL; ARTICLE; CHO CELL; CONTROLLED STUDY; DIASTOLE; ELECTROPHYSIOLOGY; GENE MUTATION; GENE OVEREXPRESSION; GENE THERAPY; GENE TRANSFER; HEART DEPOLARIZATION; HEART MUSCLE CELL; HEART VENTRICLE; HYPERPOLARIZATION; MEMBRANE POTENTIAL; NEWBORN; NONHUMAN; PACEMAKER; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN EXPRESSION; PROTEIN MOTIF; RAT; RNA TRANSCRIPTION; VIRAL GENE DELIVERY SYSTEM;

ADENOVIRIDAE; ANIMALS; ANIMALS, NEWBORN; BIOLOGICAL CLOCKS; CHO CELLS; CRICETINAE; ELECTRIC CONDUCTIVITY; GENETIC VECTORS; HEART; ION CHANNELS; MUSCLE PROTEINS; MUTATION; MYOCARDIAL CONTRACTION; PATCH-CLAMP TECHNIQUES; RATS;

EID: 0037469231     PISSN: 00097322     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.CIR.0000045672.32920.CB     Document Type: Article

References (23)

1. f) to generation of spontaneous activity in rabbit sino-atrial node myocytes. J Physiol Lond. 1991;434:23-40.
2. f) in ventricular myocytes from normal and failing human hearts. Circulation. 1998;97:55-65.
3. f, in ventricular myocytes from human failing heart. Circulation. 1997;95:568-571.
4. DiFrancesco D. Pacemaker mechanisms in cardiac tissue. Annu Rev Physiol. 1993;55:455-472.
5. Noma A. Ionic mechanisms of the cardiac pacemaker potential. Jpn Heart J. 1996;37:673-682.
6. Campbell DL, Rasmusson RL, Strauss HC. Ionic current mechanisms generating vertebrate primary cardiac pacemaker activity at the single cell level: an integrative view. Annu Rev Physiol. 1992;54:279-302.
7. Irisawa H, Brown HF, Giles W. Cardiac pacemaking in the sinoatrial node. Physiol Rev. 1993;73:197-227.
8. Ludwig A, Zong X, Jeglitsch M, et al. A family of hyperpolarization-activated mammalian cation channels. Nature. 1998;393:587-591.
9. Santoro B, Liu DT, Yao H, et al. Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. Cell. 1998;93:717-729.
10. Shi W, Wymore R, Yu H, et al. Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissues. Circ Res. 1999;85:e1-e6.
11. Ludwig A, Zong X, Stieber J, et al. Two pacemaker channels from human heart with profoundly different activation kinetics. EMBO J. 1999;18:2323-2329.
12. Chen S, Wang J, Siegelbaum SA. Properties of hyperpolarization-activated pacemaker current defined by coassembly of hcn1 and hcn2 subunits and basal modulation by cyclic nucleotide. J Gen Physiol. 2001;117:491-504.
13. Ulens C, Tytgat J. Functional heteromerization of HCN1 and HCN2 pacemaker channels. J Biol Chem. 2001;276:6069-6072.
14. Proenza C, Tran N, Angoli D, et al. Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels. J Biol Chem. 2002;277:29634-29642.
15. Xue T, Marban E, Li RA. Dominant-negative suppression of HCN1- and HCN2-encoded pacemaker currents by an engineered HCN1 construct: insights into structure-function relationships and multimerization. Circ Res. 2002;90:1267-1273.
16. Hoppe UC, Marbán E, Johns DC. Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer. J Clin Invest. 2000;105:1077-1084.
17. Hoppe UC, Marbán E, Johns DC. Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1. Proc Natl Acad Sci U S A. 2001;98:5335-5340.
18. Hardy S, Kitamura M, Harris-Stansil T, et al. Construction of adenovirus vectors through Cre-lox recombination. J Virol. 1997;71:1842-1849.
19. Johns DC, Marx R, Mains RE, et al. Inducible genetic suppression of neuronal excitability. J Neurosci. 1999;19:1691-1697.
20. Qu J, Barbuti A, Protas L, et al. HCN2 overexpression in newborn and adult ventricular myocytes: distinct effects on gating and excitability. Circ Res. 2001;89:E8-E14.
21. Hamill OP, Marty A, Neher E, et al. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981;391:85-100.
22. No D, Yao TP, Evans RM. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci U S A. 1996;93:3346-3351.
23. Zaza A, Micheletti M, Brioschi A, et al. Ionic currents during sustained pacemaker activity in rabbit sino-atrial myocytes. J Physiol (Lond). 1997;505:677-688.