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http://purl.uniprot.org/citations/15687126http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15687126http://www.w3.org/2000/01/rdf-schema#comment"

Background

The pacemaker current I(f) is present in atrial and ventricular myocytes. However, it remains controversial whether I(f) overexpression in diseased states might play a role for arrhythmogenesis, because first I(f) activation in whole-cell recordings hardly overlapped the diastolic voltage of working myocardium.

Methods and results

To obtain further insight into I(HCN) and I(f) properties, we provide for the first time detailed single-channel analysis of heterologously expressed hyperpolarization-activated cyclic nucleotide-gated (HCN) isoforms and native human I(f). HCN subtypes differed significantly in single-channel amplitude, conductance, and activation kinetics. Interestingly, threshold potentials of HCN isoforms were more positive than would have been expected from whole-cell measurements. Single-channel properties of cells cotransfected with HCN2 and HCN4 were distinct from cells expressing HCN2 or HCN4 alone, demonstrating that different HCN isoforms can influence current properties of a single HCN channel complex, thus providing direct functional evidence for HCN heteromerization. Pooled data of homomeric and heteromeric HCN channels and of native I(f) extrapolated from maximum likelihood fits indicated a multistate gating scheme comprising 5 closed- and 4 open-channel states. Single-channel characteristics of I(f) in human atrial myocytes closely resembled those of HCN4 or HCN2+HCN4, supporting the hypothesis that native I(f) channels in atrial myocardium are heteromeric complexes composed of HCN4 and/or HCN2. Most interestingly, half-maximal activation of single-channel atrial I(f) (-68.3+/-4.9 mV; k=-9.9+/-1.5; n=8) was well within the diastolic voltage range of human atrial myocardium.

Conclusions

These observations support a potential contribution of HCN/I(f) to the arrhythmogenesis of working myocardium under pathological conditions."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.org/dc/terms/identifier"doi:10.1161/01.cir.0000153799.65783.3a"xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/author"Michels G."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/author"Khan I."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/author"Herzig S."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/author"Sudkamp M."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/author"Hoppe U.C."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/author"Er F."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/pages"399-404"xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/title"Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias."xsd:string
http://purl.uniprot.org/citations/15687126http://purl.uniprot.org/core/volume"111"xsd:string
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